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(b) This composite picture of the actin cytoskeleton in a resting platelet shows the different
arrangements of microfilaments. Beneath the plasma membrane ( ) lies a two-dimensional network of filaments ( ) crosslinked by spectrin. Filamin organizes the filaments into a threedimensional gel ( ), forming the cortex of... | {
"Header 1": "**18**",
"Header 2": "Actin Polymerization Is Regulated by Proteins That Bind G-Actin",
"token_count": 2045,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Unraveling the mechanism of myosin-powered movement was greatly aided by development of in vitro motility assays. In one such assay, the sliding-filament assay, the movement of fluorescence-labeled actin filaments along a bed of myosin molecules is observed in a fluorescence microscope. Because the myosin molecules are... | {
"Header 1": "**18**",
"Header 2": "Myosin Heads Walk Along Actin Filaments in Discrete Steps",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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(a) After myosin molecules are adsorbed onto the surface of a glass coverslip, excess myosin is removed; the coverslip then is placed myosin-side down on a glass slide to form a chamber through which solutions can flow. A solution of actin filaments, made visible by staining with rhodamine-labeled phalloidin, is allowe... | {
"Header 1": "**18**",
"Header 2": "Myosin Heads Walk Along Actin Filaments in Discrete Steps",
"Header 3": "**▲ EXPERIMENTAL FIGURE 19-17** Sliding-filament assay is used to detect myosin-powered movement.",
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The flow
▲ **FIGURE 19-19 Cytoplasmic streaming in cylindrical giant algae.** (a) The center of a *Nitella* cell is filled with a single large water-filled vacuole, which is surrounded by a layer of moving cytoplasm (indicated by blue arrows). A nonmoving layer of cortical cytoplasm fil... | {
"Header 1": "**18**",
"Header 2": "Myosin Heads Walk Along Actin Filaments in Discrete Steps",
"Header 3": "**▲ EXPERIMENTAL FIGURE 19-17** Sliding-filament assay is used to detect myosin-powered movement.",
"token_count": 2044,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Like many cellular processes, skeletal muscle contraction is initiated by an increase in the cytosolic $\text{Ca}^{2^+}$ concentration. As described in Chapter 7, the $\text{Ca}^{2^+}$ concentration of the cytosol is normally kept low, below 0.1 $\mu\text{M}$ . In nonmuscle cells, $\text{Ca}^{2^+}$ ATPases in th... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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In addition, Rho kinase directly activates myosin by phosphorylating the regulatory light chain. Note that Ca<sup>2+</sup> plays no role in the regulation of myosin activity by Rho kinase.
#### **KEY CONCEPTS OF SECTION 19.3**
#### Myosin-Powered Cell Movements
- All myosin isoforms can interact with actin filame... | {
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**Cell Body Translocation** After the forward attachments have been made, the bulk contents of the cell body are translocated forward (see Figure 19-26). How this translocation is accomplished is unknown; one speculation is that the nucleus and the other organelles are embedded in the cytoskeleton and that myosin-dep... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
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Extracellular signals are transmitted across the plasma membrane by receptors specific for different factors. One set of growth factors induces actin polymerization at the leading edge through a Rac- and Cdc42-dependent pathway (*left*); another set of factors acts downstream through a Rho-dependent pathway to
migrat... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 2047,
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These two types of cytoskeletal fibers are
#### ▲ **EXPERIMENTAL FIGURE 19-31 Staining with fluorochrome-tagged antibodies reveals cellular distribution of keratin and lamin intermediate filaments.** In this fluorescent micrograph of a PtK2 cell doubly stained with anti-keratin and ant... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 2021,
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Because of their characteristic distributions, IF proteins are useful in the diagnosis and treatment of certain tumors. In a tumor, cells lose their normal
appearance, and thus their origin cannot be identified by their morphology. However, tumor cells retain many of the differentiat... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
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Later in mitosis (telophase), removal of these phosphates by specific phosphatases promotes lamin reassembly, which is critical to reformation of a nuclear envelope around the daughter chromosomes. The opposing actions of kinases and phosphatases thus provide a rapid mechanism for controlling the assembly state of lami... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 2004,
"source_pdf": "datasets/websourc... |
Transgenic mice that express a mutant K14 protein in the basal stem cells of the epidermis display gross skin abnormalities, primarily blistering of the epidermis, that resemble the human skin disease *epidermolysis bullosa simplex* (EBS). Histological examination of the blistered area reveals a high incidence of dead ... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 2038,
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What is the purpose of nonmuscle contractile bundles?
- 10. Contraction of both skeletal and smooth muscle is triggered by an increase in cytosolic $Ca^{2+}$ . Compare the mechanisms by which each type of muscle converts a rise in $Ca^{2+}$ into contraction.
- 11. Several types of cells utilize the actin cytoskeleto... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 2035,
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Myosin VI, an actin motor for membrane traffic and cell migration. *Traffic* **3**:851–858.
Field, C., R. Li, and K. Oegema. 1999. Cytokinesis in eukaryotes: a mechanistic comparison. *Curr. Opin. Cell Biol.* **11**:68–80.
Gregorio, C. C., H. Granzier, H. Sorimachi, and S. Labeit. 1999. Muscle assembly: a titanic a... | {
"Header 1": "**18**",
"Header 2": "Contraction of Skeletal Muscle Is Regulated by Ca<sup>2+</sup> and Actin-Binding Proteins",
"Header 3": "▲ FIGURE 19-29 Role of signal-transduction pathways in cell locomotion and the organization of the cytoskeleton.",
"token_count": 1000,
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A 3-second time lapse movie captures the kinesin-powered movement of a vesicle along a microtubule. [From N. Pollack et al., 1999, *J. Cell Biol.* 147:493–506; courtesy of R. D. Vale.]
n Chapter 19, we looked at microfilaments and intermediate filaments—two of the three types of cytosk... | {
"Header 1": "20 MICROTUBULES",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Perhaps the protein carrying out these ancestral functions in bacteria was modified in the course of evolution to fulfill the diverse roles of microtubules in eukaryotes.
Each tubulin subunit binds two molecules of GTP. One GTP-binding site, located in -tubulin, binds GTP irreversibly and does not hydrolyze it. The s... | {
"Header 1": "20 MICROTUBULES",
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After incorporation of a dimeric subunit into a microtubule, the GTP on the -tubulin (but not on the -tubulin) is hydrolyzed to GDP. If the rate of polymerization is faster than the rate of GTP hydrolysis, then a cap of GTP-bound subunits is generated at the () end, although the bulk of -tubulin in a microtubule will c... | {
"Header 1": "20 MICROTUBULES",
"token_count": 1953,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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bound αβ-tubulin subunits (red) add preferentially to the (+) end of a preexisting microtubule. After incorporation of a subunit, the GTP (red dot) bound to the β-tubulin monomer is hydrolyzed to GDP. Only microtubules whose (+) ends are associated with GTP-tubulin (those with a GTP cap) are stable and can serve as pri... | {
"Header 1": "20 MICROTUBULES",
"Header 3": "◀ FIGURE 20-11 Dynamic instability model of microtubule growth and shrinkage. GTP-",
"token_count": 2017,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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However, when plant or animal cells are exposed to low concentrations of colcemid, the microtubules remain and the cells become "blocked" at **meta-** **phase,** the mitotic stage at which the duplicated chromosomes are fully condensed (see Figure 9-3). When the treated cells are washed with a colcemid-free solution, c... | {
"Header 1": "20 MICROTUBULES",
"Header 3": "◀ FIGURE 20-11 Dynamic instability model of microtubule growth and shrinkage. GTP-",
"token_count": 1995,
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This location is consistent with a role for
#### ▲ **EXPERIMENTAL FIGURE 20-15 The -tubulin ring complex (-TuRC) is localized to one end of the microtubule.** (a) A fluorescence micrograph (*left*) and an electron micrograph (*right*) of microtubules stained with gold-labeled antibodies... | {
"Header 1": "20 MICROTUBULES",
"Header 3": "◀ FIGURE 20-11 Dynamic instability model of microtubule growth and shrinkage. GTP-",
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Within cells, proteins, organelles, and other membrane-limited vesicles, organelles, and proteins are frequently transported distances of many micrometers along well-defined routes in the cytosol and delivered to particular addresses. Diffusion alone cannot account for the rate, directionality, and destinations of such... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "20.2 Kinesin- and Dynein-Powered Movements",
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A neuron must constantly supply new materials—proteins and membranes—to an axon terminal to replenish those lost in the exocytosis of neurotransmitters at the junction (synapse) with another cell. Because proteins and membranes are synthesized only in the cell body, these materials must be transported down the axon, wh... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
"token_count": 2016,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Because this direction corresponds to anterograde transport, kinesin I is implicated as a motor protein that mediates anterograde axonal transport.
#### **Most Kinesins Are Processive (**-**) End–Directed Motor Proteins**
To date, approximately 10 different kinesin subfamilies have been identified. All contain a gl... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Cell Biol.* **147:**307.]
transit of Golgi vesicles to the centrosome, and some other (-) end–directed movements. Dyneins are exceptionally large, multimeric proteins, with molecular weights exceeding 1 10<sup>6</sup> . They are composed of two or three heavy chains complexed with a poorly determined number of interm... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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*Radial spokes,* which radiate from the central singlets to each A tubule of the outer doublets, are proposed to regulate dynein.
Permanently attached periodically along the length of the A tubule of each doublet microtubule are *inner-arm* and *outer-arm* dyneins (see Figure 20-25a). These axonemal dyneins are compl... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
"token_count": 2014,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### **Microtubule Dynamics and Motor Proteins in Mitosis 20.3**
**Mitosis** is the process that partitions newly replicated chromosomes equally into separate parts of a cell. The last step in the cell cycle, mitosis takes about 1 hour in an actively dividing animal cell (see Figure 1-17). In that period, the cell ... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
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In regard to their attachment to microtubules and movement, chromosomes differ substantially from the vesicle and organelle cargoes transported along cytosolic microtubules. The linkage of metaphase chromosomes to the () ends of kinetochore microtubules is mediated by a large protein complex, the kinetochore, which has... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
"token_count": 1942,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Sometimes the (+) end of a microtubule directly contacts a kinetochore, scoring a "bull's-eye." More commonly, a kinetochore contacts the side of a microtubule and then slides along the microtubule to the (+) end in a process that includes cytosolic dynein and mitotic kinesins
▲ **EXPE... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "Axonal Transport Along Microtubules Is in Both Directions",
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poleward in anaphase A. Fibroblasts are injected with fluorescent tubulin and then allowed to enter metaphase so that all the microtubules are fluorescent. Only the kinetochore microtubules are shown. In early anaphase, a band of microtubules (yellow box) is subjected to a laser light, which bleaches the fluorescence b... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "▲ EXPERIMENTAL FIGURE 20-39 Shortening at the (+) end of kinetochore microtubules moves chromosomes",
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One hypothesis is that astral or spindle microtubules send a signal to the region of the cortex midway between asters. This signal promotes the interaction of actin microfilaments and myosin II, resulting in the formation of the contractile ring followed by the development of the cleavage furrow. The signal is uniden... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "▲ EXPERIMENTAL FIGURE 20-39 Shortening at the (+) end of kinetochore microtubules moves chromosomes",
"token_count": 1904,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### **KEY TERMS**
anaphase *838* asters *840* axonal transport *829* axoneme *836* basal body *836* centriole cycle *841* centromere *838* centrosome *825* cytokinesis *848* dynamic instability *822* dyneins *829* kinesins *829*
kinetochores *840* metaphase *838* microtubule-associated proteins (MAPs) *823* micr... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "▲ EXPERIMENTAL FIGURE 20-39 Shortening at the (+) end of kinetochore microtubules moves chromosomes",
"token_count": 2041,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Dynactin polices two-way organelle traffic. *J. Cell Biol.* **160**:291–293.
Dietz, S., W. R. Schief, and J. Howard. 2002. Molecular motors: single-molecule recordings made easy. *Curr. Biol.* **12**:R203–R205.
Dujardin, D. L., and R. B. Vallee. 2002. Dynein at the cortex. *Curr. Opin. Cell Biol.* **14**:44–49.
D... | {
"Header 1": "20 MICROTUBULES",
"Header 2": "▲ EXPERIMENTAL FIGURE 20-39 Shortening at the (+) end of kinetochore microtubules moves chromosomes",
"token_count": 1537,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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This cultured rat kidney cell in metaphase shows condensed chromosomes (blue), microtubules of the spindle apparatus (red), and the inner nuclear envelope protein POM121 (green). The POM121 staining demonstrates that the inner nuclear envelope proteins retract into the ER during mitosis.... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"token_count": 2005,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Figure 21-2 outlines the role of the three major classes of cyclin-CDK complexes that control passage through the cell cycle: the G1, S-phase, and mitotic cyclin-CDK complexes. When cells are stimulated to replicate, G1 cyclin-CDK complexes are expressed first. These prepare the cell for the S phase by activating tra... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"token_count": 2031,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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The budding yeast *Saccharomyces cerevisiae* and the distantly related fission yeast *Schizosaccharomyces pombe* have been especially useful for isolation of mutants that are blocked at specific steps in the cell cycle or that exhibit altered regulation of the cycle. In both of these yeasts, **temperaturesensitive mu... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
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"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Step : Fertilization by sperm releases eggs from their metaphase arrest, allowing them to proceed through anaphase of meiosis II and undergo a second highly asymmetrical cell division that eliminates one chromatid of each chromosome in a second polar body. Step : The resulting haploid female pronucleus fuses with the h... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"token_count": 1986,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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#### **Cyclin B Levels and Kinase Activity of Mitosis-Promoting Factor (MPF) Change Together in Cycling** *Xenopus* **Egg Extracts**
Some unusual aspects of the synchronous cell cycles in early *Xenopus* embryos provided a way to study the role of mitotic cyclin in controlling MPF activity. First, following fertili... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"token_count": 2016,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Once the specificity factor is inhibited in G<sub>1</sub>, the concentration of mitotic cyclin increases, eventually reaching a high enough level to stimulate entry into the subsequent mitosis.
Biochemical studies with *Xenopus* egg extracts showed that at the time of their degradation, wild-type B-type cyclins are m... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"token_count": 1555,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Temperature-sensitive mutations in cdc2, one of several different *cdc* genes in *S. pombe*, produce opposite phenotypes depending on whether the mutation is recessive or dominant (Figure 21-12). Recessive mutations (cdc2<sup>-</sup>) give rise to abnormally long cells, whereas dominant mutations ( $cdc2^{D}$ ) give ri... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "A Highly Conserved MPF-like Complex Controls Entry into Mitosis in *S. pombe*",
"token_count": 967,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Analysis of additional *S. pombe cdc* mutants revealed that proteins encoded by other genes regulate the protein kinase activity of the mitotic cyclin-CDK complex (MPF) in fission yeast. For example, temperature-sensitive *cdc25*<sup>-</sup> mutants are delayed in entering mitosis at the nonpermissive temperature, prod... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 2029,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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At present it is clear that MPF activity in *S. pombe* is regulated in a complex fashion in order to control precisely the timing of mitosis and therefore the size of daughter cells.
Enzymes with activities equivalent to *S. pombe* Wee1 and Cdc25 have been found in cycling *Xenopus* egg extracts. The *Xenopus* Wee1 t... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 2021,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Because the transfected *lamin* genes are expressed at much higher levels than the endogenous hamster *lamin* gene, most of the lamin A produced in transfected cells is human lamin A. Transfected cells at various stages in the cell cycle then were stained with a
fluorescent-labeled monoclonal antibody specific for hu... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 2012,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Cohesin SMC proteins bind to each sister chromatid; other subunits of cohesin, including *Scc1,* then link the SMC proteins, firmly associating the two chromatids. The cross-linking activity of cohesin depends on *securin,* which is found in all eukaryotes. Prior to anaphase, securin binds to and inhibits separase, a u... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 1919,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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This activates separase, which cleaves a subunit of cohesin, thereby unlinking sister chromatids (see Figure 21-19).
- After sister chromatids have moved to the spindle poles, the APC is directed by Cdh1 to polyubiquitinate mitotic cyclins, leading to their destruction and causing the decrease in MPF activity that mark... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 1967,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Sequencing of the three *CLN* genes showed that they encoded related proteins each of which includes an ≈100-residue region exhibiting significant homology with B-type cyclins from sea urchin, *Xenopus*, human, and *S. pombe.* This region encodes the cyclin domain that interacts with CDKs and is included in the domain ... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Phosphorylation of the CDK Subunit Regulates the Kinase Activity of MPF",
"token_count": 1986,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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As the S-phase cyclin-CDK heterodimers accumulate in late $G_1$ , they are immediately inactivated by binding of an inhibitor, called Sic1, that is expressed late in mitosis and in early $G_1$ . Because Sic1 specifically inhibits B-type cyclin-CDK complexes, but has no effect on the $G_1$ cyclin-CDK complexes, it f... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Degradation of the S-Phase Inhibitor Triggers DNA Replication",
"token_count": 560,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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As budding yeast cells progress through the S phase, they begin transcribing genes encoding two additional B-type cyclins, Clb3 and Clb4. These form heterodimeric cyclin-CDK complexes that, together with complexes including Clb5 and Clb6, activate DNA replication origins throughout the remainder of the S phase. The Clb... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Multiple Cyclins Direct the Kinase Activity of *S. cerevisiae* CDK During Different Cell-Cycle Phases",
"token_count": 1934,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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By analogy with cyclindependent kinases (CDKs), which must be bound by a partner cyclin to activate their protein kinase activity, the *D*bf4 *d*ependent *k*inase Cdc7 is often called *DDK.* Although the complete set of proteins that must be phosphorylated to activate initiation of DNA synthesis has not yet been determ... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Multiple Cyclins Direct the Kinase Activity of *S. cerevisiae* CDK During Different Cell-Cycle Phases",
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Most studies of mammalian cell-cycle control have been done with cultured cells that require certain polypeptide growth factors (mitogens) to stimulate cell proliferation. Binding of these growth factors to specific receptor proteins that span the plasma membrane initiates a cascade of signal transduction that ultimate... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Mammalian Restriction Point Is Analogous to START in Yeast Cells",
"token_count": 1983,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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Mutant, unregulated forms of both c-Fos and c-Jun are expressed by oncogenic retroviruses (Chapter 23); the discovery that the viral forms of these proteins (v-Fos and v-Jun) can transform normal cells into cancer cells led to identification of the regulated cellular forms of these transcription factors.
After peakin... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Mammalian Restriction Point Is Analogous to START in Yeast Cells",
"token_count": 1661,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
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High levels of E2Fs activate transcription of the *cyclin A* gene as mammalian cells approach the $G_1 \rightarrow S$ transition. (Despite its name, cyclin A is a B-type cyclin, not a $G_1$ cyclin;
see Table 21-1.) Disruption of cyclin A function inhibits DNA synthesis in mammalian cells, suggesting that cyclin A... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis",
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Cyclins A and B are polyubiquitinated by the anaphase-promoting complex (APC) during late anaphase and then are degraded by proteasomes.
- The activity of mammalian mitotic cyclin-CDK complexes also are regulated by phosphorylation and dephosphorylation similar to the mechanism in *S. pombe*, with the Cdc25C phosphatas... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis",
"token_count": 2004,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
(The SPB, from which spindle microtubules originate, is equivalent to the centrosome in higher eukaryotes.) At the SPB, Tem1 is maintained in the inactive GDP-bound state by a specific GAP (GTPaseaccelerating protein). The GEF (guanosine nucleotide– exchange factor) that activates Tem1 is localized to the cortex of the... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis",
"token_count": 2017,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Three types of tumor-suppressor proteins (ATM/ATR, Chk1/2, and p53) are critical to this checkpoint.
- Activation of the ATM or ATR protein kinases in response to DNA damage due to UV light or $\gamma$ -irradiation leads to arrest in $G_1$ and the S phase via a pathway that leads to loss of Cdc25A phosphatase activi... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Cyclin A Is Required for DNA Synthesis and CDK1 for Entry into Mitosis",
"token_count": 204,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
In *S. cerevisiae* and *S. pombe*, depletion of nitrogen and carbon sources induces diploid cells to undergo meiosis, yielding haploid spores (see Figure 1-5). This process is analogous to
▶ FIGURE 21-34 Meiosis. Premeiotic cells have two copies of each chromosome (2n), one derived from the paternal parent and one fr... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Repression of G<sub>1</sub> Cyclins and Meiosis-Specific Ime2 Prevents DNA Replication in Meiosis II",
"token_count": 2026,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
One of the multiple genes found to be expressed in *S. cerevisiae* cells during meiosis but not during mitosis is *MAM1,* which encodes a protein called *monopolin.* Subsequent gene-specific mutagenesis studies revealed that deletion of *MAM1* causes sister chromatids in metaphase of meiosis I to associate with the fir... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Repression of G<sub>1</sub> Cyclins and Meiosis-Specific Ime2 Prevents DNA Replication in Meiosis II",
"token_count": 2024,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
What is the wee phenotype? What did the characterization of the *wee1* gene tell us about cell cycle control?
- **4.** Tim Hunt shared the 2001 Nobel Prize for his work in the discovery and characterization of cyclin proteins in eggs and embryos. What experimental evidence indicates that cyclin B is required for a cell... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Repression of G<sub>1</sub> Cyclins and Meiosis-Specific Ime2 Prevents DNA Replication in Meiosis II",
"token_count": 1944,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Why do the *cdc28*ts cells form colonies at 25 °C but not 37 °C? What is the significance of colony formation of the *cdc28*ts maize *cdc2* cells at 37 °C? What does this experiment tell us about the functional homology of cyclindependent kinase genes am... | {
"Header 1": "REGULATING THE EUKARYOTIC CELL CYCLE",
"Header 2": "Repression of G<sub>1</sub> Cyclins and Meiosis-Specific Ime2 Prevents DNA Replication in Meiosis II",
"token_count": 1703,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Cells being born in the developing cerebellum. All nuclei are labeled in red; the green cells are dividing and migrating into internal layers of the neural tissue. [Courtesy of Tal Raveh, Matthew Scott, and Jane Johnson.]
uring the evolution of multicellular organisms, new mechanisms a... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 2047,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
However, a whole series of cell divisions is not required; a single division of a pluripotent precursor cell can yield distinct progeny. For instance, lineage studies in which cells are marked by stable infection with a detectable retrovirus have shown that neurons and glial cells can arise from a single division of a ... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 2038,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
At later times, the labeled cells are seen progressively farther away from their point of birth in the crypt. Cells at the top are shed. This process ensures contant replenishment of the gut epithelium with new cells. [Part (a) adapted from C. S. Potten, 1998, *Philos. Trans. R. Soc. London, Ser. B* **353**:821. Part (... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 2045,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
As demonstrated experimentally in sheep, each of the cells has the potential to give rise to a complete animal. Additional divisions produce a mass, composed of ≈64 cells, that separates into two cell types: trophectoderm, which will form extraembryonic tissues like the placenta, and the *inner cell mass,* which gives ... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 2027,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
The bilateral symmetry of the worm implies duplication of lineages on the two sides; curiously, though, functionally equivalent cells on each side can arise from a pattern of division that is different on the two sides. Some of the embryonic cells function as stem cells, dividing repeatedly to form more of themselves... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 2028,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
By definition, all other cells are somatic cells.
- Embryonic development of *C. elegans* begins with asymmetric division of the fertilized egg (zygote). The lineage of all the cells in adult worms is known and is highly reproducible (see Figure 22-9).
- Short regulatory RNAs control the timing of developmental cell di... | {
"Header 1": "22",
"Header 2": "CELL BIRTH, LINEAGE, AND DEATH",
"token_count": 736,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Each of the three *S. cerevisiae* cell types expresses a unique set of regulatory genes that is responsible for all the differences among the three cell types. All haploid cells express certain haploidspecific genes; in addition, a cells express a-specific genes, and $\alpha$ cells express $\alpha$ -specific genes. ... | {
"Header 1": "22",
"Header 2": "Transcription Factors Encoded at the *MAT* Locus Act in Concert with MCM1 to Specify Cell Type",
"token_count": 687,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
In a cells, homodimeric MCM1 binds to the so-called P box sequence in the upstream regulatory sequences (URSs) of a-specific genes, stimulating their transcription (Figure 22-12a). Transcription of $\alpha$ -specific genes is controlled by two adjacent sequences—the P box and the Q box—located in the URSs associated w... | {
"Header 1": "22",
"Header 2": "MCM1 and $\\alpha$ 1-MCM1 Complexes Activate Gene Transcription",
"token_count": 505,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Highly specific binding occurs as a consequence of the interaction of $\alpha$ 2 with other transcription factors at different sites in DNA. Flanking the P box in each a-specific URS are two $\alpha$ 2-binding sites. Both MCM1 and $\alpha$ 2 can bind independently to an **a**-specific URS with relatively low affinit... | {
"Header 1": "22",
"Header 2": "$\\alpha$ 2-MCM1 and $\\alpha$ 2-a1 Complexes Repress Transcription",
"token_count": 423,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
An important feature of the yeast life cycle is the ability of haploid **a** and $\alpha$ cells to mate, that is, attach and fuse giving rise to a diploid $\mathbf{a}/\alpha$ cell (see Figure 1-5). Each haploid cell type secretes a different mating factor, a small polypeptide pheromone, and expresses a cell-surface... | {
"Header 1": "22",
"Header 2": "Pheromones Induce Mating of $\\alpha$ and a Cells to Generate a Third Cell Type",
"token_count": 1006,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
As indicated by global expression patterns, yeast cells of different mating types are still rather similar. Developmental
biologists do not yet know the complete set of molecules that distinguishes any one cell type (e.g., muscle) from all the other cell types in a multicellular organism. The extensive cell specifica... | {
"Header 1": "22",
"Header 2": "22.3 Specification and Differentiation of Muscle",
"token_count": 2033,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
The observation that 1 in 104 cells transfected with this DNA was converted into a myotube is consistent with the hypothesis that one or a small set of closely linked genes is responsible for converting fibroblasts into myotubes.
Subsequent studies led to the isolation and characterization of four different but relat... | {
"Header 1": "22",
"Header 2": "22.3 Specification and Differentiation of Muscle",
"token_count": 2016,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Chromatin immunoprecipitation experiments with antibodies against acetylated histone H4 show that the acetylated histone level associated with MEF2-regulated genes is higher in differentiated myotubes than in myoblasts (see Figure 11-31). The role of histone deacetylases in muscle development was revealed in experiment... | {
"Header 1": "22",
"Header 2": "22.3 Specification and Differentiation of Muscle",
"token_count": 2032,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
In both cases, the proteins encoded by the earliest-acting genes (*left*) are under both positive and negative control by other related proteins (blue type). [Adapted from Y. N. Jan and L. Y. Jan, 1993, *Cell* **75**:827.]
 ... | {
"Header 1": "22",
"Header 2": "22.3 Specification and Differentiation of Muscle",
"token_count": 1285,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
$S.\ cerevisiae$ cells use a remarkable mechanism to control the differentiation of the cells as the cell lineage progresses. Whether a haploid yeast cell exhibits the $\alpha$ or a mating type is determined by which genes are present at the MAT locus (see Figure 22-11). As described in Chapter 11, the MAT locus in ... | {
"Header 1": "22",
"Header 2": "Yeast Mating-Type Switching Depends upon Asymmetric Cell Division",
"token_count": 710,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
റ
0
NNECTIONS
CONNECTIONS
► FIGURE 22-22 Model for restriction of matingtype switching to mother cells in S. cerevisiae. Ash1 protein prevents a cell from transcribing the HO gene whose encoded protein initiates the DNA rearrangement that results in mating-type switching from **a** to $\alpha$ or $\alpha$ to... | {
"Header 1": "ASH1 mRNA Localization",
"token_count": 565,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
epidermal cells and neural cells. Neuroblasts, the stem cells for the nervous system, are formed when ectoderm cells enlarge, separate from the ectodermal epithelium, and move into the interior of the embryo (2–4). Each neuroblast that arises divides asymmetrically to recreate itself and produce a ganglion mother cell ... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2019,
"source_pdf": "datas... |
The protein Lethal giant larvae (Lgl), a component of the Scrib/Dlg/Lgl asymmetry pathway, helps to localize Miranda basally in fly neuroblasts.
Lgl binds to myosin II, which functions in cytokinesis (see Figure 19-20). Lgl itself is uniformly localized around the cortex. Lgl is phosphorylated by the apical complex a... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2013,
"source_pdf": "datas... |
In the early 1900s the number of neurons innervating the periphery was shown to depend upon the size of the tissue to which they would connect, the so-called "target field." For instance, removal of limb buds from the developing chick embryo leads to a reduction in the number of sensory neurons and motoneurons innerv... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2025,
"source_pdf": "datas... |
The human Bcl-2 protein and worm CED-9 protein are homologous, and a *bcl-2* transgene can
▲ **EXPERIMENTAL FIGURE 22-30 Mutations in the** *ced-3* **gene block programmed cell death in** *C. elegans.* (a) Newly hatched larva carrying a mutation in the... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2036,
"source_pdf": "datas... |
The finding that trophic factors appear to work largely independent of protein synthesis suggested that these external signals lead to changes in the activities of preexisting proteins rather than to activation of gene expression. Scientists demonstrated that in the absence of trophic factors, the nonphosphorylated for... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2030,
"source_pdf": "datas... |
A tumor may contain a mixture of cells, some capable of seeding new tumors or continued uncontrolled growth, and some capable only of growing in place or for a limited time. In this sense the tumor has its own stem cells, and they must be found and studied, so they become vulnerable to our medicine. One option is to ma... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2040,
"source_pdf": "datas... |
Identification of spatial and temporal cues that regulate postembryonic expression of axon maintenance factors in the *C. elegans* ventral nerve cord. *Development* **130**:599–610.
Bach, S. P., A. G. Renehan, and C. S. Potten. 2000. Stem cells: the intestinal stem cell as a paradigm. *Carcinogenesis* **21**:469–476.... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 2056,
"source_pdf": "datas... |
Highly coordinated gene regulation in mouse skeletal muscle regeneration. *J. Biol. Chem.* **278**:8826–8836.
#### Regulation of Asymmetric Cell Division
Adler, P. N., and J. Taylor. 2001. Asymmetric cell division: plane but not simple. *Curr. Biol.* **11**:R233–236.
Ben-Yehuda, S., and R. Losick. 2002. Asymmetri... | {
"Header 1": "ASH1 mRNA Localization",
"Header 2": "► FIGURE 22-23 Asymmetric cell division during *Drosophila* neurogenesis. The ectodermal sheet (■) of the early embryo gives rise to both enidermal cells and neural cells. Neurophysis, the stem cells for the nervous",
"token_count": 1773,
"source_pdf": "datas... |
A blood smear from a person with acute myelogenous leukemia. The gigantic cells with irregularly shaped purple nuclei are leukemia cells. The small reddish-gray circular cells are normal red blood cells. [Margaret Cubberly/Phototake.]
ancer causes about one-fifth of the deaths in the U... | {
"Header 1": "23",
"Header 2": "**CANCER**",
"token_count": 1994,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
When these tumors progress, the cells invade surrounding tissues, get into the body's circulatory system, and establish secondary areas of proliferation, a process called **metastasis.** Most malignant cells eventually acquire the ability to metastasize. Thus the major characteristics that differentiate metastatic (or ... | {
"Header 1": "23",
"Header 2": "**CANCER**",
"token_count": 2025,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
The progeny of the affected cell are more rounded and less adherent to one another and to the dish than are the normal surrounding cells, forming a three-dimensional cluster of cells (a focus) that can be recognized under the microscope (Figure 23-3b). Such cells, which continue to grow when the normal cells have becom... | {
"Header 1": "23",
"Header 2": "**CANCER**",
"token_count": 2032,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Studies on colon cancer provide the most compelling evidence to date for the multi-hit model of cancer induction. Surgeons can obtain fairly pure samples of many human cancers, but generally the exact stage of tumor progression cannot be identified and analyzed. An exception is colon cancer, which evolves through disti... | {
"Header 1": "23",
"Header 2": "Successive Oncogenic Mutations Can Be Traced in Colon Cancers",
"token_count": 2029,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Apoptotic proteins (V) include tumor suppressors that promote apoptosis and oncoproteins that promote cell survival. Virusencoded proteins that activate signal receptors (Ia) also can induce cancer.
#### **Gain-of-Function Mutations Convert Proto-oncogenes into Oncogenes**
Recall that... | {
"Header 1": "23",
"Header 2": "Successive Oncogenic Mutations Can Be Traced in Colon Cancers",
"token_count": 2007,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Unlike retroviral oncogenes, which are derived from normal cellular genes and have no function for the virus except to allow their proliferation in tumors, the known oncogenes of DNA viruses are integral parts of the viral genome and are required for viral replication. As discussed later, the oncoproteins expressed fro... | {
"Header 1": "23",
"Header 2": "Successive Oncogenic Mutations Can Be Traced in Colon Cancers",
"token_count": 667,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
tumors in retina
▲ FIGURE 23-10 Role of spontaneous somatic mutation in retinoblastoma. This disease is marked by retinal tumors that arise from cells carrying two mutant $RB^-$ alleles. (a) In hereditary (familial) retinoblastoma, a child inherits a normal $RB^+$ allele from one pa... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"token_count": 2032,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
For example, *APC*, the critical first gene mutated on the path to colon carcinoma, is now known to be part of the Wnt signaling pathway, which led to the discovery of the involvement of *-catenin* mutations in colon cancer. Mutations in tumorsuppressor developmental genes promote tumor formation
in tissues where the... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"token_count": 1940,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Similarly, human tumors called multiple endocrine neoplasia type 2 produce a constitutively active dimeric Gliaderived neurotrophic factor (GDNF) receptor that results
#### **Exterior Cytosol** Neu oncoprotein **Exterior Cytosol** Inactive receptor tyrosine kinase Her2 receptor EGF receptor **Proto-oncogene receptor ... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"token_count": 2043,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Constitutive Ras activation can also arise from a recessive loss-of-function mutation in a GTPase-accelerating protein (GAP). The normal GAP function is to accelerate hydrolysis of GTP and the conversion of active GTP-bound Ras to inactive GDP-bound Ras (see Figure 3-29). The loss of GAP leads to sustained Ras activa... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"token_count": 2019,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
As discussed in Chapter 21, c-Fos and c-Myc stimulate transcription of genes encoding proteins that promote progression through the G1 phase of the cell cycle and the G1 to S transition. In tumors, the oncogenic forms of these or other transcription factors are frequently expressed at high and unregulated levels.
In ... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"token_count": 983,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Normal growth and development depends on a finely tuned, highly regulated balance between growth-promoting and growth-inhibiting pathways. Mutations that disrupt this balance can lead to cancer. Most of the mutations discussed in the previous section cause inappropriate activity of growth-promoting pathways. Just as cr... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "23.4 Mutations Causing Loss of Growth-Inhibiting and Cell-Cycle Controls",
"token_count": 2048,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Transgenic flies were constructed to overexpress E2F, which resulted in mild growth defects. A search for mutations that increase the effect of the *E2F* overexpression in these flies identified three components of the Swi/Snf complex. That loss of function of these genes increases the proliferative effects of E2F indi... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "23.4 Mutations Causing Loss of Growth-Inhibiting and Cell-Cycle Controls",
"token_count": 291,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
A critical feature of cell-cycle control is the $G_1$ checkpoint, which prevents cells with damaged DNA from entering the
▲ **EXPERIMENTAL FIGURE 23-22 Mutations in human tumors that inactivate the function of p53 protein are highly concentrated in a few residues.** Colored boxes repr... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "Loss of p53 Abolishes the DNA-Damage Checkpoint",
"token_count": 2013,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Cells lacking PTEN phosphatase have elevated levels of phosphatidylinositol 3,4,5-trisphosphate and active protein kinase B, which promotes cell survival and prevents apoptosis by several pathways. Thus PTEN acts as a pro-apoptotic tumor suppressor by decreasing the anti-apoptotic effect of protein kinase B.
The most... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "Loss of p53 Abolishes the DNA-Damage Checkpoint",
"token_count": 2037,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
DNA is continually subjected to a barrage of damaging chemical reactions; estimates of the number of DNA damage events in a single human cell range from $10^4$ to $10^6$ per day! Even if DNA were not exposed to damaging chemicals, DNA is inherently unstable. For example, the bond connecting a purine base to deoxyri... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "Chemical Damage to DNA Can Lead to Mutations",
"token_count": 315,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
Environmental chemicals were originally associated with cancer through experimental studies in animals. The classic experiment is to repeatedly paint a test substance on the back of a mouse and look for development of both local and systemic tumors in the animal. Likewise, the ability of ionizing radiation to cause hum... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "Some Carcinogens Have Been Linked to Specific Cancers",
"token_count": 2025,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
But since a G · T mismatch is almost invariably caused by chemical conversion of C to U or 5-methyl C to T, the repair system "knows" to remove the T and replace it with a C. The G · T mismatch is recognized by a DNA glycosylase that flips the thymine base out of the helix and then hydrolyzes the bond that connects it ... | {
"Header 1": "(a) Hereditary retinoblastoma Somatic mutation Somatic retinal cell dives rise to",
"Header 2": "Some Carcinogens Have Been Linked to Specific Cancers",
"token_count": 2032,
"source_pdf": "datasets/websources/biochem/s-molecularcellbiology.pdf"
} |
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