Input: These results suggest that the IRE motif in the ALAS mRNA is functional and imply that translation of the mRNA is controlled by cellular iron availability during erythropoiesis.

IRE motif

ALAS mRNA

mRNA


Input: Regulation of jun and fos gene expression in human monocytes by the macrophage colony-stimulating factor.

human monocytes

macrophage colony-stimulating factor


Input: The macrophage colony-stimulating factor (M-CSF) is required for the growth and differentiation of mononuclear phagocytes.

macrophage colony-stimulating factor

M-CSF

mononuclear phagocytes


Input: However, the signaling events responsible for these effects remain unclear.


Input: The present studies have examined the effects of M-CSF on potential signaling pathways involving expression of the jun and fos early response genes.

M-CSF


Input: Low levels of c-jun transcripts were detectable in resting human peripheral blood monocytes.

c-jun transcripts

resting human peripheral blood monocytes


Input: Treatment of these cells with 10(3) units/ml human recombinant M-CSF was associated with rapid and transient increases in c-jun mRNA levels.

human recombinant

M-CSF

c-jun mRNA


Input: Nuclear run-on assays and mRNA stability studies demonstrated that M-CSF regulates c-jun expression by both an increase in transcription rate and a prolongation in the half-life of c-jun transcripts.

M-CSF

c-jun

c-jun transcripts


Input: M-CSF treatment was also associated with a rapid induction of the jun-B gene, although expression of this gene was prolonged compared to that of c-jun.

M-CSF

jun-B gene

c-jun


Input: We further demonstrate that M-CSF increases c-fos mRNA levels in human monocytes through control at both the transcriptional and posttranscriptional levels.

M-CSF

c-fos mRNA

human monocytes


Input: Maximal induction of the c-fos gene was followed by that for the fos-B gene.

c-fos gene

fos-B gene


Input: Moreover, M-CSF -induced expression of the fos-related gene, fra-1, was delayed compared to that for both c-fos and fos-B.

M-CSF

fos-related gene

c-fos

fos-B


Input: Taken together, the results indicate that M-CSF treatment is associated with differential activation of multiple members of the jun/fos family and that expression of these genes could contribute to nuclear signaling mechanisms that regulate a specific program of monocyte differentiation.

M-CSF

jun/fos family


Input: Glucocorticoid receptors in systemic lupus erythematosus.

Glucocorticoid receptors


Input: Glucocorticosteroids remain the major treatment modality for systemic lupus erythematosus (SLE ), but their mechanism of action is unclear.


Input: Over the past decade it has become clear that glucocorticosteroid receptors play a significant role in the mechanism of glucocorticosteroid action.

glucocorticosteroid receptors


Input: We studied glucocorticosteroid receptor density and affinity on peripheral blood mononuclear cells by the glucocorticosteroid binding assay in 33 patients with SLE who had taken no glucocorticosteroid for the previous 6 months and in 32 healthy controls.

glucocorticosteroid receptor

peripheral blood mononuclear cells


Input: Patients' disease activity was measured by the SLE Disease Activity Index (SLEDAI ).


Input: Glucocorticosteroid receptors on leukocytes of patients with SLE were significantly higher than in healthy controls (4419 +/- 306 vs 3369 +/- 196, p less than 0.005).

Glucocorticosteroid receptors

leukocytes


Input: The binding affinity was not different between patients and controls.


Input: There was no correlation between glucocorticosteroid receptor number and SLE disease activity.

glucocorticosteroid receptor


Input: Kappa B binding proteins are constitutively expressed in an IL-2 autocrine human T cell line.

Kappa B binding proteins

IL-2 autocrine human T cell line


Input: The IL-2 and the IL-2-R alpha genes are both expressed transiently in normal T lymphocytes after Ag or mitogen activation.

normal T lymphocytes


Input: In contrast, the human T cell line, IARC 301, expresses these two genes constitutively and we have previously demonstrated that its growth depends on the autocrine production of this T cell growth factor and high affinity IL-2R.

human T cell line

IARC 301

T cell growth factor

high affinity IL-2R


Input: To dissect the molecular basis for the unusual persistent expression of the IL-2 and IL-2-R alpha genes in these IARC 301 T cells, we have analyzed the interactions of constitutively expressed nuclear proteins with the 5' flanking regions of the IL-2 and IL-2-R alpha genes using both DNase I footprinting and gel retardation techniques.

IARC 301

T cells

constitutively expressed nuclear proteins

DNase I

5' flanking regions


Input: We have found that a region in both genes (-276 to -250 for IL-2-R alpha and -203 to -183 for IL-2 ), which corresponds to a kappa B enhancer element, is specifically protected by nuclear proteins from IARC 301.

IL-2-R alpha

kappa B enhancer element,

nuclear proteins

IARC 301


Input: In agreement with this finding, both the IL-2 and IL-2-R alpha promoters are active in transient transfection assays in IARC 301 cells.

IARC 301 cells


Input: In contrast, mutation of the kappa B enhancer results in markedly attenuated activities of both promoters.

kappa B enhancer

promoters


Input: Two proteins binding the kappa B sequence, NF-kappa B and KBF1, are constitutively expressed in IARC 301 nuclei and induced by PMA and PHA in Jurkat.

kappa B sequence

NF-kappa B

PHA

IARC 301

Jurkat


Input: They bind to the kappa B motifs with different relative affinities that may reflect their different contribution in the expression of various promoters.

kappa B motifs

promoters


Input: HIV1 infection of human monocytes and macrophages promotes induction or translocation of NF-KB-related factors.

human monocytes

macrophages

NF-KB-related factors


Input: In 1991, we demonstrated, using electrophoretic mobility shift assays, that 3 different factors (termed B1, B2 and B3) with affinity for the KB-enhancer target sequence were specifically detected in nuclear extracts from HIV1 -infected monocytes and macrophages.

KB-enhancer target sequence

HIV1 -infected monocytes

macrophages


Input: The B2 factor was induced in the nuclei of these cells only upon HIV1 infection.

B2 factor


Input: The B3 factor was only slightly evident in nuclei of uninfected cells but was readily detectable in nuclei of infected monocytes.

B3 factor

uninfected cells

infected monocytes


Input: Its expression remained very low in nuclei of HIV1 -infected macrophages.

HIV1 -infected macrophages


Input: In this paper, we demonstrate that the B2 factor is expressed in the cytosol of monocytes and macrophages as a DNA-binding protein, indicating that it is not associated with an inhibitor (IKB ).

B2 factor

DNA-binding protein

monocytes

macrophages


Input: This factor remained clustered in the cytosol and was translocated to the nuclei only after HIV1 infection.


Input: The B3 factor is detected in the cytosol only when cells are HIV1 -infected.

B3 factor


Input: The role of HIV1 infection in the expression and the translocation of these factors is discussed.


Input: Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box.

T lymphocyte-specific transcription factor

sequence-specific HMG box


Input: CD3 -epsilon expression is controlled by a downstream T lymphocyte-specific enhancer element.

downstream T lymphocyte-specific enhancer element


Input: We report the identification of a T cell-specific transcription factor, TCF-1, binding to this element.

T cell-specific transcription factor


Input: The multimerized recognition motif of TCF-1 constituted a T cell-specific enhancer.

multimerized recognition motif


Input: Subsequent cloning of TCF-1 identified three splice alternatives.

splice alternatives


Input: TCF-1 contained a single DNA-binding HMG box most closely related to similar boxes in the putative mammalian sex-determining gene SRY and in the Schizosaccharomyces pombe Mc mating type gene.

DNA-binding HMG box

putative mammalian sex-determining gene

SRY

Schizosaccharomyces pombe Mc mating type gene


Input: TCF-1 mRNA was expressed uniquely in T lymphocytes.

TCF-1 mRNA

T lymphocytes


Input: Upon cotransfection into non-T cells, TCF-1 could transactivate through its cognate motif.

non-T cells


Input: These results identify TCF-1 as a T cell-specific transcription factor, which might play a role in the establishment of the mature T cell phenotype.

T cell-specific transcription factor

mature T cell phenotype


Input: Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1.

transcriptional suppressor proteins

negative regulatory element


Input: Two different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line.

negative regulatory element

NRE

virus-infected human T cell line


Input: One of the factors bound to a novel dyad symmetrical sequence.

novel dyad symmetrical sequence


Input: This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene.

promoter region

human retinoblastoma gene


Input: Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay.

virus-uninfected human T cell lines

HeLa cells


Input: The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE.

putative AP-1 recognition sequence

NRE


Input: However, this factor did not bind to a typical AP-1 site.

AP-1 site


Input: The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively.

binding site

heterologous promoter


Input: Thus, each factor may function as a novel negative regulator of transcription.

novel negative regulator


Input: Protein kinase C activation and protooncogene expression in differentiation/retrodifferentiation of human U-937 leukemia cells.

Protein kinase C

protooncogene

human U-937 leukemia cells


Input: Human U-937 leukemia cells differentiate along the monocytic lineage following 3-day exposures to 12-O-tetradecanoylphorbol-13-acetate (TPA ).

Human U-937 leukemia cells

monocytic lineage


Input: This induction of differentiation is accompanied by adherence and loss of proliferation, as well as expression/repression of differentiation-associated genes.

differentiation-associated genes


Input: Long term culture of TPA -differentiated U-937 cells in the absence of phorbol ester for 32-36 days resulted in a process of retrodifferentiation.

TPA -differentiated U-937 cells


Input: The retrodifferentiated cells detached from the substrate and reinitiated proliferation.


Input: Other cellular parameters, such as glycosidase activities, cytokine release, and filament expression, returned to levels similar to that observed in uninduced cells.

cytokine

uninduced cells


Input: Treatment of U-937 cells with TPA resulted in a rapid translocation of protein kinase C (PKC) from the cytosol to cell membrane fractions within 2-8 min.

U-937 cells

protein kinase C

PKC


Input: Increased levels of membrane-associated PKC activity persisted until 17-29 days.

PKC


Input: However, longer periods of incubation were associated with a return to the distribution of PKC in control cells.

PKC


Input: Activation of PKC has been implicated in the regulation of certain immediate early response genes, and in the present studies, TPA rapidly induced c-fos and c-jun gene expression.

PKC

immediate early response genes

c-fos

c-jun gene expression


Input: Levels of c-fos and c-jun transcripts remained elevated during periods of PKC activation and also returned to levels observed in control cells by 30-36 days, when the cells entered retrodifferentiation.

PKC


Input: Staurosporine, a nonspecific inhibitor of PKC, partially blocked TPA -induced adherence and growth inhibition and concomitantly prevented TPA-induced c-fos and c-jun gene expression.

PKC


Input: (ABSTRACT TRUNCATED AT 250 WORDS)


Input: Kappa B-specific DNA binding proteins are differentially inhibited by enhancer mutations and biological oxidation.

Kappa B-specific DNA binding proteins


Input: Kappa B (kappa B) enhancer binding proteins isolated from the nuclei of activated human T cells produce two distinct nucleoprotein complexes when incubated with the kappa B element from the interleukin-2 receptor-alpha (IL-2R alpha) gene.

Kappa B (kappa B) enhancer binding proteins

nucleoprotein complexes

IL-2R alpha

human T cells

kappa B element

interleukin-2 receptor-alpha (

) gene


Input: These two DNA-protein complexes are composed of at least four host proteins (p50, p55, p75, p85 ), each of which shares structural similarity with the v-rel oncogene product.

DNA-protein complexes

v-rel oncogene product


Input: Nuclear expression of these proteins is induced with distinctly biphasic kinetics following phorbol ester activation of T cells (p55/p75 early and p50/p85 late ).

T cells

p55/p75 early

p50/p85 late


Input: DNA-protein crosslinking studies have revealed that the more rapidly migrating B2 complex contains both p50 and p55 while the more slowly migrating B1 complex is composed of p50, p55, p75, and p85.

B2 complex

B1 complex


Input: Site-directed mutagenesis of the wild-type IL-2R alpha kappa B enhancer (GGGGAATCTCCC) has revealed that the binding of p50 and p55 (B2 complex) is particularly sensitive to alteration of the 5' triplet of deoxyguanosine residues.

wild-type IL-2R alpha kappa B enhancer

5' triplet

B2 complex


Input: In contrast, formation of the B1 complex, reflecting the binding of p75 and p85, critically depends upon the more 3' sequences of this enhancer element.

B1 complex

enhancer element


Input: DNA binding by all four of these Rel-related factors is blocked by selective chemical modification of lysine and arginine residues, suggesting that both of these basic amino acids are required for binding to the kappa B element.

Rel-related factors

kappa B element


Input: Similarly, covalent modification of free sulfhydryl groups with diamide (reversible) or N-ethylmaleimide (irreversible) results in a complete loss of DNA binding activity.


Input: In contrast, mild oxidation with glucose oxidase selectively inhibits p75 and p85 binding while not blocking p50 and p55 interactions.

glucose oxidase


Input: These findings suggest that reduced cysteine thiols play an important role in the DNA binding activity of this family of Rel-related transcription factors.

Rel-related transcription factors


Input: [Changes in leucocytic estrogen receptor levels in patients with climacteric syndrome and therapeutic effect of liuwei dihuang pills]

estrogen receptor


Input: The numbers of estrogen receptor (ER) in human peripheral leucocytes in 22 women with climacteric syndrome were measured by radioligand method.

estrogen receptor

ER

human peripheral leucocytes


Input: The results were compared with those of 12 normal child-bearing-age women.


Input: It wat found that the contents of leucocytic ER in climacteric syndrome patients were significantly lower than normal child-bearing-age women.

leucocytic

ER


Input: The authors used a Chinese prescription -- Liuwei Dihuang Pills (LDP) to treat the patients for 2 months.


Input: The numbers of leucocytic ER were significantly increased after treatment.

leucocytic

ER


Input: The data indicate that decrease of ER levels in cell may involve in the pathogenesis of climacteric syndrome.

ER


Input: LDP not only increases plasma estradiol levels, but also increases the leucocytic ER levels.

ER


Input: This may be the basis of the therapeutic effect on the disease.


Input: Evaluation of the role of ligand and thermal activation of specific DNA binding by in vitro synthesized human glucocorticoid receptor.

in vitro synthesized human glucocorticoid receptor


Input: We have used a DNA-binding/immunoprecipitation assay to analyze the capacity of human glucocorticoid receptor (hGR ), generated in rabbit reticulocyte lysates, to bind DNA.

human glucocorticoid receptor

hGR


Input: In vitro translated hGR was indistinguishable from native hGR, as determined by migration on sodium dodecyl sulfate-polyacrylamide gels, sedimentation on sucrose density gradients, and reactivity with antipeptide antibodies generated against hGR.

In vitro translated hGR

native hGR

antipeptide antibodies

hGR


Input: In addition, cell-free synthesized hGR was capable of specific binding to glucocorticoid response element (GRE )-containing DNA fragments.

cell-free synthesized hGR

glucocorticoid response element (

GRE )-containing DNA fragments


Input: Using this assay system, we have evaluated the contributions of ligand binding and heat activation to DNA binding by these glucocorticoid receptors.

glucocorticoid receptors


Input: In vitro translated hGR was capable of selective DNA binding even in the absence of glucocorticoid.

In vitro translated hGR


Input: Treatment with dexamethasone or the antiglucocorticoid RU486 had no additional effect on the DNA-binding capacity when receptor preparations were maintained at 0 C (no activation).


Input: In contrast, addition of either ligand or antagonist in combination with a heat activation step promoted DNA binding by approximately 3-fold over that of heat-activated unliganded receptors.

unliganded receptors


Input: Agonist (dexamethasone) was slightly more effective in supporting specific DNA binding than antagonist (RU486 ).


Input: DNA binding by in vitro synthesized GR was blocked by the addition of sodium molybdate to the receptor preparations before steroid addition and thermal activation.

in vitro synthesized GR


Input: Addition of KCl resulted in less DNA binding either due to blockage of DNA- receptor complex formation or disruption of the complexes.

receptor complex


Input: The specificity of DNA binding by cell-free synthesized hGR was analyzed further by examining the abilities of various DNAs to compete for binding to a naturally occurring GRE found in the mouse mammary tumor virus-long terminal repeat.

cell-free synthesized hGR

various DNAs

GRE

mouse mammary tumor virus-long terminal repeat


Input: Oligonucleotides containing the consensus GRE were the most efficient competitors, and fragments containing regulatory sequences from glucocorticoid -repressible genes were somewhat competitive, whereas single stranded oligonucleotides were unable to compete for mouse mammary tumor virus-long terminal repeat DNA binding, except when competitor was present at extremely high concentrations.

consensus

GRE

regulatory sequences

glucocorticoid -repressible genes

mouse mammary tumor virus-long terminal repeat


Input: Together these studies indicate that hGR synthesized in rabbit reticulocyte lysates displays many of the same properties, including GRE -specific DNA binding, observed for glucocorticoid receptor present in cytosolic extracts of mammalian cells and tissues.

hGR

glucocorticoid receptor

GRE

mammalian cells


Input: Similarities between the effects of dexamethasone and RU486 suggest that the antiglucocorticoid properties of RU486 do not occur at the level of specific DNA binding.


Input: Expression of 1,25(OH)2D3 receptors on alveolar lymphocytes from patients with pulmonary granulomatous diseases.

1,25(OH)2D3 receptors

alveolar lymphocytes


Input: 1,25(OH)2D3 is known to be produced at sites of granulomatous reactions.


Input: In order to characterize the cell types that are targets for this immunoregulatory hormone, we have evaluated the expression of 1,25(OH)2D3 receptors on peripheral blood T-lymphocytes and those recovered from the lung by bronchoalveolar lavage from patients with pulmonary granulomatous diseases (tuberculosis and sarcoidosis) and from normal control subjects using combined autoradiographic and immunohistochemical techniques.

1,25(OH)2D3 receptors

peripheral blood T-lymphocytes


Input: Lavage T-lymphocytes from patients with tuberculosis or with sarcoidosis, but not those from normal control subjects, expressed 1,25(OH)2D3 receptors as demonstrated by binding of [3H]1,25(OH)2D3, which was inhibited by the presence of excess unlabeled 1,25(OH)2D3, but not by the presence of unlabeled 25(OH)D3 (receptor-positive lymphocytes: sarcoidosis, 20 +/- 12%; tuberculosis, 31 +/- 17%).

1,25(OH)2D3 receptors

receptor-positive lymphocytes


Input: In contrast, blood lymphocytes from patients with granulomatous diseases did not express detectable 1,25(OH)2D3 receptors.

blood lymphocytes

1,25(OH)2D3 receptors


Input: The percentage of lavage T-lymphocytes expressing 1,25(OH)2D3 receptors was significantly greater for patients with tuberculosis presenting with isolated hilar adenopathy than for patients with pulmonary infiltrates and/or cavities.

lavage T-lymphocytes

1,25(OH)2D3 receptors


Input: 1,25(OH)2D3 receptors were expressed to a greater extent on CD8+ T-lymphocytes than on CD4+ T-lymphocytes in sarcoidosis, whereas a greater proportion of CD4+ than of CD8+ T-lymphocytes from patients with tuberculosis were receptor-positive.

1,25(OH)2D3 receptors

CD8+ T-lymphocytes

CD4+ T-lymphocytes

CD8+ T-lymphocytes


Input: These findings support the conclusion that the interaction of 1,25(OH)2D3 with its receptor on T-lymphocytes may play an important role in the regulation of granulomatous reactions, but because these receptors are expressed on different lymphocyte populations, the net effect of this potent immunoregulatory molecule is likely different in sarcoidosis and tuberculosis.

T-lymphocytes

lymphocyte populations

immunoregulatory molecule


Input: Role for the Epstein-Barr virus nuclear antigen 2 in viral promoter switching during initial stages of infection.

Epstein-Barr virus nuclear antigen 2

viral promoter


Input: During latent Epstein-Barr virus (EBV) infection of human B lymphocytes, six viral nuclear antigen (EBNAs) are expressed from long primary transcripts by means of alternative splicing and alternative polyadenylylation sites.

human B lymphocytes

six viral nuclear antigen

EBNAs

long primary transcripts

alternative splicing

alternative polyadenylylation sites


Input: These transcripts initiate from one of two promoters, Cp or Wp, that function in a mutually exclusive fashion.

promoters

Cp

Wp


Input: Wp is exclusively utilized during the initial stages of infection of primary B lymphocytes, followed by a switch to Cp usage.

Wp

Cp

primary B lymphocytes


Input: These studies have been extended to show that (i) a mutant EBV strain lacking the gene encoding EBNA 2 fails to switch from Wp to Cp usage in primary B lymphocytes, although the virus contains a functional Cp; (ii) a region from -429 to -245 base pairs upstream of Cp is essential for Cp activity in B lymphocytes, but only in the context of upstream and downstream sequences; (iii) this region contains an EBNA 2 -dependent enhancer; and (iv) DNase I protection employing nuclear extracts from B and T lymphocytes revealed a B-cell-specific footprint in the region of the EBNA 2 -dependent enhancer.

EBNA 2

EBNA 2

DNase I

Wp

Cp

Cp

-429 to -245 base pairs

Cp

Cp

upstream and downstream sequences

-dependent enhancer

B-cell-specific footprint

EBNA 2 -dependent enhancer

primary B lymphocytes

B lymphocytes


Input: These results support a model for viral promoter switching during the initial stages of infection in which Wp activity leads to the expression of EBNA 2, followed by activation of Cp through the EBNA 2 -dependent enhancer.

viral promoter

Wp

Cp

-dependent enhancer

EBNA 2

EBNA 2


Input: Immune response of peripheral blood mononuclear cells to HBx-antigen of hepatitis B virus.

peripheral blood mononuclear cells

HBx-antigen


Input: The hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg.

hepatitis B virus genome

transcriptional transactivator protein

HBxAg


Input: We have investigated whether this antigen is a target structure for human T-lymphocytes.

human T-lymphocytes


Input: Using recombinant HBxAg protein, we found HBxAg -specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals.

recombinant

HBxAg protein

HBxAg

peripheral blood mononuclear cells


Input: With HBxAg -specific synthetic polypeptides, several T-cell epitopes were identified.

HBxAg

T-cell epitopes


Input: Most were located in the carboxyterminal half of the HBxAg protein.

carboxyterminal half

HBxAg protein


Input: Five T-cell clones specific for a T-cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4-positive, CD8-negative subtype.

T-cell clones

CD2/CD4-positive, CD8-negative subtype

T-cell epitope

carboxyterminal region

HBxAg


Input: These data establish for the first time HBxAg as an antigen in the cellular immune response.

HBxAg


Input: [Changes in leucocytic estrogen receptor levels in patients with gynecomastia]

leucocytic estrogen receptor


Input: The number of estrogen receptor (ER) in human peripheral leucocytes in 13 men with gynecomastia were measured by radioligand binding method. The results were compared with those of 13 sex-and age-matched healthy subjects.

estrogen receptor

ER

human peripheral leucocytes


Input: It was found that the number of ER in leucocytes was significantly increased in gynecomastia (Rs of leucocytes were 1054 +/- 254 sites/cell).

ER

leucocytes

leucocytes


Input: It suggested that increase of ER levels play an important role in the pathogenesis of gynecomastia.


Input: The NF kappa B independent cis-acting sequences in HIV-1 LTR responsive to T-cell activation.

NF kappa B independent cis-acting sequences

HIV-1 LTR


Input: The rate of transcription initiation directed by the long terminal repeat (LTR) of HIV-1 increases in response to mitogenic stimuli of T cells.

long terminal repeat

T cells


Input: Here we show that the response of the HIV-1 LTR may be governed by two independent sequences located 5' to the site of transcription initiation sequences that bind either NFAT-1 or NF kappa B.

HIV-1 LTR

transcription initiation sequences

NF kappa B


Input: The rate of LTR -directed gene expression increased in response to treatment with either a phorbol ester or tumor necrosis factor alpha if either the NFAT-1 or NF kappa B binding sites were deleted, but failed to respond to these mitogenic stimuli if both sequences were absent.

LTR

binding sites

tumor necrosis factor alpha

NF kappa B


Input: The HIV-1 mutant virus containing both NF kappa B and NFAT-1 deletion was able to replicate although at a much decreased growth rate, while the deletion of NFAT-1 alone increased the viral growth rate in Jurkat cells.

NF kappa B

and NFAT-1 deletion

Jurkat cells


Input: Neither deletion of NF kappa B nor deletion of NFAT-1 decreased activation of viral replication by phorbol ester.

NF kappa B


Input: cAMP -dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins.

JunD

JunB

AP-1 proteins


Input: We demonstrate that JunD, a component of the AP-1 transcription factor complex, activates transcription of the human proenkephalin gene in a fashion that is completely dependent upon the cAMP-dependent protein kinase, protein kinase A.

JunD

AP-1 transcription factor complex

cAMP-dependent protein kinase

protein kinase A

human proenkephalin gene


Input: Activation of proenkephalin transcription by JunD is dependent upon a previously characterized cAMP -, phorbol ester -, and Ca(2+) -inducible enhancer, and JunD is shown to bind the enhancer as a homodimer.

JunD

JunD

homodimer

cAMP -, phorbol ester -, and Ca(2+) -inducible enhancer

enhancer


Input: Another component of the AP-1 transcription complex, JunB, is shown to inhibit activation mediated by JunD.

AP-1 transcription complex

JunB

JunD


Input: As a homodimer JunB is unable to bind the enhancer; however in the presence of c-Fos, high-affinity binding is observed.

JunB

c-Fos


Input: Furthermore, JunD is shown to activate transcription of genes linked to both cAMP and phorbol ester response elements in a protein kinase A -dependent fashion, further blurring the distinction between these response elements.

JunD

protein kinase A

response elements


Input: These results demonstrate that the transcriptional activity of an AP-1-related protein is regulated by the cAMP -dependent second-messenger pathway and suggest that JunD and other AP-1-related proteins may play an important role in the regulation of gene expression by cAMP -dependent intracellular signaling pathways.

AP-1-related protein

JunD

AP-1-related proteins


Input: [Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors in patients with deficiency-cold vs deficiency-heat syndromes]

glucocorticoid receptors


Input: Plasma cortisol concentration and blood leukocyte content of glucocorticoid receptors (GCR) were assayed in 20 patients with deficiency syndromes, 10 cold in property (deficiency-cold), the other 10 hot in property (deficiency-heat), and also in 10 healthy individuals as normal control for the purpose of investigating the nature of cold and heat syndromes.

glucocorticoid receptors

GCR


Input: As a result, the cases of deficiency-cold syndrome (DCS) had a normal concentration of plasma cortisol but a lowered content of GCR in leukocytes when compared with the normal control (P less than 0.05); the cases of deficiency-heat syndrome (DHS) had a higher concentration of plasma cortisol than the normal control (P less than 0.05) and a slightly higher content of GCR in leukocytes.

GCR

GCR

leukocytes

leukocytes


Input: It was concluded that the DCS is characterized by diminished biological effects of adrenocortical activity, while the DHS, by augmented biological effects of adrenocortical activity.


Input: The role of jun and fos gene family members in 12-O-tetradecanoylphorbol-13-acetate induced hemopoietic differentiation.


Input: Terminal differentiation of the leukemic cell lines U-937 and HL-60 by 12-O-tetradecanoylphorbol-13-acetate is accompanied by marked changes in gene expression.

leukemic cell lines


Input: In this study, we demonstrate that the expression of jun and fos gene family members is induced with variable kinetics during 12-O-tetradecanoylphorbol-13-acetate induced differentiation, with c-jun expression best paralleling differentiation.

c-jun


Input: The generation of AP-1 complexes, as measured by DNA binding activity, closely parallels morphological differentiation.

AP-1 complexes


Input: Furthermore, the ability of these complexes to regulate gene expression is demonstrated by increased transcription from an AP-1 driven reporter construct and marked increases in the expression of endogenous AP-1 regulated genes.

AP-1 driven reporter construct

endogenous AP-1 regulated genes


Input: Differentiation assays using water soluble phorbol esters reveal that differentiation becomes irreversible soon after AP-1 appears.


Input: This tight correlation between c-jun expression, the generation of AP-1 activity, and differentiation suggests a critical role for this gene and transcriptional complex during this process.

c-jun

transcriptional complex


Input: Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A [see comments]

T-cell transcription factor


Input: Cyclosporin A and FK506 inhibit T- and B-cell activation and other processes essential to an effective immune response.


Input: In T lymphocytes these drugs disrupt an unknown step in the transmission of signals from the T-cell antigen receptor to cytokine genes that coordinate the immune response.

T lymphocytes

T-cell antigen receptor

cytokine genes


Input: The putative intracellular receptors for FK506 and cyclosporin are cis-trans prolyl isomerases.

putative intracellular receptors


Input: Binding of the drug inhibits isomerase activity, but studies with other prolyl isomerase inhibitors and analysis of cyclosporin -resistant mutants in yeast suggest that the effects of the drug result from the formation of an inhibitory complex between the drug and isomerase, and not from inhibition of isomerase activity.

isomerase

isomerase

inhibitory complex

isomerase

isomerase

cyclosporin -resistant mutants


Input: A transcription factor, NF-AT, which is essential for early T-cell gene activation, seems to be a specific target of cyclosporin A and FK506 action because transcription directed by this protein is blocked in T cells treated with these drugs, with little or no effect on other transcription factors such as AP-1 and NF-kappa B.

transcription factor

NF-AT

transcription factors

NF-kappa B

T cells


Input: Here we demonstrate that NF-AT is formed when a signal from the antigen receptor induces a pre-existing cytoplasmic subunit to translocate to the nucleus and combine with a newly synthesized nuclear subunit of NF-AT.

NF-AT

antigen receptor

NF-AT


Input: FK506 and cyclosporin A block translocation of the cytoplasmic component without affecting synthesis of the nuclear subunit.

cytoplasmic component

nuclear subunit


Input: Glucocorticoid receptors in lymphocytes in anorexia nervosa.

Glucocorticoid receptors

lymphocytes


Input: OBJECTIVE: The aim was to explore the down-regulation of the glucocorticoid receptors during hypercortisolaemia in anorexia nervosa.

glucocorticoid receptors


Input: DESIGN: Urine and plasma samples were obtained for cortisol determination and blood lymphocytes were isolated for receptor binding studies.

blood lymphocytes


Input: PATIENTS: Sixteen anorexic patients, aged 16-27 years, with a mean +/- SEM body mass index of 14.2 +/- 2.0 (ranging from 11.1 to 17.4), and 15 normal women were studied.


Input: Six patients were reinvestigated after a significant weight gain.


Input: MEASUREMENTS: The binding capacity and affinity of the glucocorticoid receptors were measured with dexamethasone as ligand on lymphocytes.

glucocorticoid receptors

lymphocytes


Input: RESULTS: In patients, both total and free plasma cortisol concentrations were higher than in the normal women, as was their urinary free cortisol; the number of glucocorticoid receptors per cell (Ro) and the binding affinity (Kd) for dexamethasone were, however, not significantly different (Ro: 7687 +/- 1750 vs 7347 +/- 1285 sites/cell; Kd: 7.7 +/- 2.4 vs 7.4 +/- 1.7 nM at 24 degrees C).

glucocorticoid receptors


Input: After weight gain (14 +/- 2 to 16 +/- 2 kg/m2), receptor numbers were 8421 +/- 2126 (pre) and 9011 +/- 500 (post) sites/cell, which are not significantly different (P greater than 0.2); the Kd was unchanged (9.3 +/- 2.6 vs 9.2 +/- 2.4 nM).


Input: CONCLUSIONS Hypercortisolaemia does not down-regulate the lymphocyte glucocorticoid receptors in anorexia nervosa and a post-receptor defect might be involved in peripheral tissue resistance to the effects of glucocorticoid hormones in undernutrition.

glucocorticoid receptors


Input: Inhibition of protein phosphatases by okadaic acid induces AP1 in human T cells.

protein phosphatases

human

T cells


Input: To examine the role of protein phosphatases in T cell activation, Jurkat cells were treated with okadaic acid, an inhibitor of type 1 and 2A phosphatases, and nuclear extracts were examined for the presence of AP1 as a measure of early T cell activation.

protein phosphatases

Jurkat cells


Input: Okadaic acid was found to be a potent inducer of AP1.


Input: In contrast to phorbol esters such as phorbol myristate acetate (PMA ), the induction of AP1 by okadaic acid occurs predominantly by transcriptional activation of the jun and fos family of proto-oncogenes.

proto-oncogenes


Input: Surprisingly, while the addition of phytohemagglutinin further enhanced the induction of AP1, the addition of PMA inhibited it.

phytohemagglutinin


Input: Okadaic acid treatment was found to dramatically increase mRNA transcripts of the jun family of proto-oncogenes including c-jun, junD, and junB and to a lesser extent the fos family including c-fos and fra-1.

mRNA transcripts

jun family of proto-oncogenes

c-jun

junD

junB

fos family

c-fos


Input: By comparison, PMA is a very inefficient inducer of the jun gene family in Jurkat cells.

jun gene family

Jurkat cells


Input: Similar to its effect on the induction of AP1 by okadaic acid, PMA inhibits the induction of c-jun mRNA by okadaic acid.

c-jun mRNA


Input: Transfection of c-jun promoter constructs confirmed the marked difference between PMA and okadaic acid in inducing c-jun transcription.

c-jun promoter constructs

c-jun


Input: The induction of AP1 by okadaic acid suggests that protein phosphatases 1 and 2A (PP1 and PP2A) may be involved in T cell activation as important negative regulators of the transcription factor AP1.

transcription factor


Input: Cloning of murine TCF-1, a T cell-specific transcription factor interacting with functional motifs in the CD3-epsilon and T cell receptor alpha enhancers.

murine TCF-1

transcription factor

functional motifs


Input: CD3 -epsilon gene expression is confined to the T cell lineage.

T cell lineage


Input: We have recently identified and cloned a human transcription factor, TCF-1, that binds to a functional element in the T lymphocyte-specific enhancer of CD3-epsilon.

human transcription factor


Input: In a panel of human cell lines, TCF-1 expression was restricted to T lineage cells.

T lineage cells


Input: TCF-1 belonged to a novel family of genes that contain the so-called high mobility group 1 (HMG) box.

mobility group 1 (HMG) box


Input: Here we report the cloning of murine TCF-1.

murine


Input: Two splice alternatives were identified that were not previously observed in human TCF-1.

human TCF-1


Input: Murine and human TCF-1 displayed a 95.5% overall amino acid homology.


Input: Recombinant murine and human TCF-1 recognized the same sequence motif in the CD3-epsilon enhancer as judged by gel retardation and methylation interference assays.

CD3-epsilon enhancer


Input: With the murine cDNA clones several aspects of TCF-1 were analyzed.

murine cDNA clones


Input: First, deletion analysis revealed that a region of TCF-1 containing the HMG box was sufficient for sequence-specific binding.

HMG box


Input: Second, by high stringency Northern blotting and in situ hybridization, TCF-1 expression was shown to be confined to the thymus and to the T cell areas of the spleen.


Input: Third, TCF-1 bound specifically to a functional T cell-specific element in the T cell receptor alpha (TCR-alpha) enhancer.

T cell-specific element

T cell receptor alpha (TCR-alpha) enhancer


Input: The T lineage-specific expression and the affinity for functional motifs in the TCR-alpha and CD3-epsilon enhancers imply an important role for TCF-1 in the establishment of the mature T cell phenotype.

functional motifs

mature T cell phenotype


Input: Cloning of a human homeobox gene that resembles a diverged Drosophila homeobox gene and is expressed in activated lymphocytes.

human homeobox gene

diverged Drosophila homeobox gene

lymphocytes


Input: A new homeobox gene, HB24, has been isolated from a human B-lymphocyte cDNA library.

homeobox gene

human B-lymphocyte cDNA library


Input: Northern blot analysis of polyadenylated RNA purified from activated human B cells revealed a single mRNA transcript of approximately 2.3 kb.

polyadenylated RNA

single mRNA transcript

activated human B cells


Input: Two cDNA clones were sequenced and provided 2,250 nucleotides (nt) of DNA sequence information.

cDNA clones

DNA sequence