Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression and function of several proto-oncogenes were examined in a human acute T cell leukemia line, JURKAT, during phorbol ester-induced terminal differentiation. Treating JURKAT cells with the phorbol ester tetradecanoyl phorbol acetate (TPA) inhibited their proliferation and induced expression of the gene for the interleukin 2 receptor alpha chain (IL2R-alpha), consistent with previous reports. In unstimulated proliferating JURKAT cells, high levels of C-MYC, N-RAS, and BCL2 mRNAs were found that diminished rapidly following TPA-induced cessation of growth. In contrast, accumulation of mRNAs for the C-FOS, C-JUN, and EGR-1 genes increased markedly in TPA-treated cells and preceded the induction of IL2R-alpha mRNA. Expression of C-MYB, C-RAF-1, C-LCK, C-FYN, and C-FGR proto-oncogenes was relatively unchanged. To explore directly the function of two of these protooncogenes in regulating the growth of JURKAT T cells, we stably transferred C-MYC and BCL2 expression plasmids into these cells. Despite sustained expression of C-MYC, BCL2, or the combination of these protooncogenes, TPA continued to inhibit JURKAT cell growth and to induce IL2R expression. Thus, although C-MYC and BCL2 proto-oncogene expression correlated with proliferation in TPA-treated JURKAT cells, continuous over-expression of even the combination of these oncogenes was insufficient for abrogating the effects of TPA in these leukemic T cells. Because human lymphoid malignancies frequently contain chromosomal translocations that deregulate the expression of C-MYC and BCL2, our findings could have relevance for attempts to induce terminal differentiation of leukemic cells by in vitro exposure of patients' bone marrow cells to phorbol esters.
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PMID:Phorbol ester-mediated inhibition of growth and regulation of proto-oncogene expression in the human T cell leukemia line JURKAT. 201 1

Antiserum raised against a Fos peptide (amino acids Lys-127 to Arg-140 of chicken c-Fos) recognizes a 46-kDa Fos-related protein in cell lysates of growth-stimulated chicken embryo fibroblasts. Induction of the 46-kDa protein is transient but is slightly prolonged relative to c-Fos following growth stimulation. Using a mixed oligonucleotide probe encoding the peptide antigen, we have cloned the chicken genomic locus that encodes this protein and have determined its gene structure. This locus consists of four exons, each of which has some homology with the corresponding exons of the chicken c-fos gene, and it expresses a 6-kilobase mRNA after growth stimulation. The deduced amino acid sequence of the gene (323 amino acids) contains a "leucine zipper" and includes five distinct regions that exhibit strong sequence homology to the recently identified fos-related antigens Fra-1 (rat) and FosB (mouse) as well as c-Fos. Since the other regions of the gene have little homology to any of these three proteins, this gene was named "fra-2." When the fra-2 gene was overexpressed by an avian retrovirus vector, it caused transformation of chicken embryo fibroblasts. The fra-2 gene product formed a complex in cells with the c-Jun protein, indicating that c-fos and fra-2 share biological and biochemical functions.
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PMID:Isolation and characterization of fra-2, an additional member of the fos gene family. 211 Mar 68

Lesion of the sciatic nerve caused a rapid increase in c-fos and c-jun mRNA that was followed about 2 hr later by an increase in nerve growth factor (NGF) mRNA. To evaluate whether the initial increase in c-fos mRNA is causally related to the subsequent increase in NGF mRNA, we performed experiments with fibroblasts of transgenic mice carrying an exogenous c-fos gene under the control of a metallothionein promoter. In primary cultures of these fibroblasts, CdCl2 evoked a rapid increase in exogenous c-fos mRNA, followed immediately by an increase in endogenous c-jun mRNA and with a slight delay by an increase in NGF mRNA. In fibroblasts of C3H control mice, CdCl2 had no effect on the mRNA levels of the protooncogenes c-fos and c-jun or of NGF. Additional evidence for a causal relationship between c-fos induction and the subsequent increase in NGF mRNA was obtained in cotransfection experiments. Fibroblasts of C3H control mice were cotransfected with a metallothionein-promoter-driven c-fos expression vector and a NGF promoter-chloramphenicol acetyltransferase reporter gene construct. Induction of the exogenous c-fos by CdCl2 resulted in increased activity of the NGF promoter. DNase I footprint experiments demonstrated that a binding site for transcription factor AP-1 (Fos/Jun heterodimer) in the first intron of the NGF gene was protected following c-fos induction. That this protected AP-1 site indeed was functional in the regulation of NGF expression was verified by deletion experiments and by a point mutation in the corresponding AP-1 binding region in the NGF promoter-chloramphenicol acetyltransferase reporter construct.
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PMID:Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. 211 Oct 20

The proximal region of the ovalbumin gene promoter contains a half-palindromic estrogen-responsive element (ERE) that mediates cell-specific trans-activation by the estrogen receptor (ER). We show that the ovalbumin ERE binds a ubiquitous nucleoprotein complex containing oncoproteins c-Fos and c-Jun. Mutations altering the estrogen inducibility of the promoter prevent the complex formation, which is, however, found in the presence and absence of ER and estradiol. Mutagenesis indicates that the sequence 5'-TGGGTCA-3', containing the half-palindromic ERE, is responsible for induction by phorbol esters of the ovalbumin promoter and is a target for c-fos and c-jun trans-activation. Transfection experiments reveal that c-fos, c-jun, and ER coactivate the ovalbumin promoter. Direct ER interaction with the target sequence is not required, since an ER deleted for its DNA binding domain is functional in the coactivation with c-fos and c-jun. Our data indicate a convergence of hormonal induction and activation of signal transduction pathways at the transcriptional level.
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PMID:Activation of the ovalbumin gene by the estrogen receptor involves the fos-jun complex. 212 18

In an extensive screen of a cDNA library prepared from serum-stimulated mouse NIH 3T3 cells, we identified three distinct jun-related clones. Two of them were carrying c-jun and junB sequences respectively, whereas the sequence of the third group of clones (junD) was distinct from these two and from v-jun. The amino acid sequences derived from these jun-related clones are very well conserved in five distinct regions including the putative DNA binding domain. Truncated c-Jun and JunD proteins containing the C-terminus recognize the same DNA sequences which were defined as the PEA1/AP1 binding sequence or TPA response element (TRE). Furthermore, both can trans-activate a promoter including the TRE, and this activation is further enhanced by c-fos. Contrary to c-jun and junB transcription, which are strongly stimulated by serum or TPA treatment of quiescent 3T3 cells, junD transcription is not significantly stimulated in these conditions. The tissue distribution and levels of expression of junD mRNA differ from that of c-jun and junB mRNA. These observations suggest that each of these Jun-related gene products has a distinct role in the control of gene activity and growth in the organism.
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PMID:Characterization of junD: a new member of the jun proto-oncogene family. 250 80

Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.
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PMID:trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. 251 30

We have investigated the mechanism of stimulation of thyroglobulin gene expression by thyrotropin (TSH) and cAMP in rat thyroid FRTL-5 cells. In contrast to the c-fos gene, induction of the thyroglobulin gene by TSH or cAMP is slow (10 h) and sensitive to cycloheximide treatment. We have identified a TSH and cAMP-responsive region of thyroglobulin gene between - 171 and - 140 base pairs from the transcription initiation site. The hormone-responsive region contains DNA sequence elements similar to the consensus cAMP-responsive element as well as the transcription factor AP-1-binding site but with opposite sequence polarity. Three DNA-protein complexes are formed when the hormone-responsive region is incubated with nuclear extracts of FRTL-5 cells. Formation of these complexes is dependent on TSH or cAMP stimulation, thus suggesting that the factors involved in binding to the hormone-responsive region may be induced by TSH. Although the identity of these factors is not yet known, they do not appear to be related to either cAMP-responsive element-binding protein or AP-1. These results suggest that thyroglobulin gene expression in FRTL-5 cells may be mediated by nuclear factors that are induced by cAMP in contrast to other genes (e.g. c-fos) whose activation involves post-translational modification of the pre-existing proteins specific for cAMP-responsive element.
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PMID:Induction of nuclear protein factors specific for hormone-responsive region during activation of thyroglobulin gene by thyrotropin in rat thyroid FRTL-5 cells. 254 Jan 96

Administration of convulsant doses of Metrazole (pentylenetetrazol) and picrotoxin, as well as maximal electroshock, results in a rapid but transient increase in c-fos mRNA in mouse brain. Elevation of c-fos mRNA is followed by the accumulation and subsequent disappearance of Fos, the protein encoded by c-fos. In addition, immunoblots reveal the induction of two additional proteins that are antigenically related to Fos (Fra, Fos-related antigens). Fos and the various Fra appear and disappear in a staggered manner over an 8 hour period, such that at longer times after stimulation the brain contains no Fos but relatively large amounts of Fra (the latter being designated here by their apparent molecular weights, Fra-46K and Fra-35K). Previous studies have established that Fos, as well as several Fra, contribute to transcription factor AP-1 nucleoprotein complexes along with Jun, the product of the jun proto-oncogene. The appearance in brain of Fos and Fra coincides with a protracted increase in total AP-1 DNA binding activity, indicating that all the Fos-like proteins can participate in AP-1 complexes. Furthermore, the molecular composition of these complexes alters with time after stimulation. The induction of c-fos by Metrazole is blocked or attenuated by known anticonvulsants such as diazepam and valproate as well as the N-methyl-D-aspartate (NMDA) receptor antagonists, 2-amino-5-phosphonovaleric acid (APV) and MK-801. This suggests that fos induction might involve stimulation of a glutamate receptor. This conclusion was strengthened by the observations that two glutamate receptor agonists, kainic acid and NMDA, induced c-fos expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamate receptor agonists increase the expression of Fos, Fra, and AP-1 DNA binding activity in the mammalian brain. 255 94

Treatment of adenovirus-infected mouse S49 cells with cAMP analogs leads to the transcriptional induction of early viral genes. E1A proteins and cAMP work in synergy to activate several of these genes. We now demonstrate that the transcription factor AP-1 is modestly induced by cAMP in S49 cells and induced to significantly higher levels by cAMP in the presence of E1A proteins. Cytoplasmic levels of c-fos and junB mRNAs are rapidly increased by cAMP, and the induction is substantially stronger in the presence of E1A protein. The AP-1 activity binds efficiently to both AP-1 and activating transcription factor (ATF)/cAMP response element binding protein (CREB)-binding sites present in E1A-inducible promoters and presumably plays a role in the transcriptional activation of adenovirus genes by E1A proteins and cAMP.
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PMID:Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP. 255 73

Interleukin-1 (IL-1) is a major regulator of inflammation and immunity. IL-1 induces T lymphocyte growth by acting as a second signal (together with antigen) in enhancing the production of interleukin-2 (IL-2). An IL-1-responsive element in the promoter region of the human IL-2 gene was similar to the binding site for the transcription factor AP-1. IL-1 enhanced expression of c-jun messenger RNA, whereas the antigenic signal enhanced messenger RNA expression of c-fos. Thus, the two components of the AP-1 factor are independently regulated and the AP-1 factor may serve as a nuclear mediator for the many actions of IL-1 on cells.
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PMID:Interleukin-1 costimulatory activity on the interleukin-2 promoter via AP-1. 279 85


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