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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Fos protein complex and several Fos-related antigens (FRA) bind specifically to a sequence element referred to as the HeLa cell activator protein 1 (AP-1) binding site. A combination of structural and immunological comparisons has identified the Fos-associated protein (p39) as the protein product of the jun proto-oncogene (c-Jun). The p39/Jun protein is one of the major polypeptides identified in AP-1 oligonucleotide affinity chromatography extracts of cellular proteins. These preparations of AP-1 also contain Fos and several FRA's. Some of these proteins bind to the AP-1 site directly whereas others, like Fos, appear to bind indirectly via protein-protein interactions. Cell-surface stimulation results in an increase in c-fos and c-jun products. Thus, the products of two protooncogenes (and several related proteins), induced by extracellular stimuli, form a complex that associates with transcriptional control elements containing AP-1 sites, thereby potentially mediating the long-term responses to signals that regulate growth control and development.
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PMID:Fos-associated protein p39 is the product of the jun proto-oncogene. 313 Jun 60

Cell lines stably transfected with metal inducible, MT-fos chimeric genes were used to study the ability of the c-fos gene product, Fos, to act as a transcriptional trans-activator. In 3T3MTfos cells, induction of Fos expression led to specific trans-activation of an AP-1 responsive reporter gene. Induction of Fos expression in F9MTfos cells, however, did not lead to trans-activation. Since, unlike NIH3T3 cells, F9 cells do not contain detectable levels of AP-1, we examined whether a c-Jun/AP-1 expression vector can restore the trans-activating effect of Fos in F9MTfos cells. Transfection with a functional c-Jun/AP-1 vector restored the specific trans-activating effect of Fos on AP-1 responsive constructs. When incubated with nondenatured cell extracts, anti-cFos antisera precipitated a protein complex composed of Fos and several Fos associated proteins (FAP). One of these, FAP p39, is structurally identical to c-Jun/AP-1. These results suggest that Fos is a trans-acting factor that is capable of stimulating gene expression not by direct binding to DNA but by interaction with the sequence-specific transcription factor AP-1. Therefore recognition of specific cis-elements by AP-1 is a prerequisite for Fos-mediated stimulation of gene expression.
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PMID:The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. 313 40

Some growth factor-induced genes, such as the c-fos gene, are activated rapidly and transiently without intervening protein synthesis. Others, like the rat transin gene, are activated more slowly but more durably and their activation requires prior protein synthesis. It is tempting to speculate that certain rapidly-activated genes code for transcription factors which interact directly with promoter regions of genes like the transin gene to trigger their expression. Unfortunately, little is known about the majority of primary response genes to support this hypothesis. The proto-oncogene c-jun codes for the transcription factor AP-1 or a closely related protein. We show that epidermal growth factor stimulates transcription of the c-jun gene in fibroblasts as a primary response. This supports the notion that increased expression of genes encoding transcription factors is an important element of the signal transduction mechanism, assuring the long-term transcriptional response of cells to growth factors.
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PMID:Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. 313 98

The c-Jun and c-fos proto-oncogenes encode proteins that form a complex which regulates transcription from promoters containing AP-1 activation elements. c-Jun has specific DNA binding activity, while c-Fos has homology to the putative DNA binding domain of c-Jun. Following in vitro translation, c-Jun binds as a homodimer to the AP-1 DNA site, while c-Fos fails to dimerize and displays no apparent affinity for the AP-1 element. Cotranslated c-Jun and c-Fos proteins bind 25 times more efficiently to the AP-1 DNA site as a heterodimer than does the c-Jun homodimer. These experiments suggest that in growth factor-stimulated cells c-Jun binds DNA as a dimer with c-Fos as its natural partner. However, overexpression of c-Jun protein in the absence of c-Fos may result in formation of aberrant homodimeric transcription complexes, which could abrogate the normal mechanisms controlling gene expression.
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PMID:c-Jun dimerizes with itself and with c-Fos, forming complexes of different DNA binding affinities. 314 92

Mouse 3T3 fibroblasts lacking c-fos were employed to demonstrate an essential function of the UV-inducible transcription factor AP-1 (Fos/Jun) in the response to the cytotoxic effects of short-wavelength ultraviolet (UVC) radiation. Clonogenic survival and proliferation of cells lacking c-fos were drastically reduced following UV irradiation. This UV hypersensitivity manifests itself primarily in increased cell death, partly by apoptosis, and prolonged recovery time from UV-induced cell cycle arrest. Co-culture with wild-type cells did not ameliorate the hypersensitivity of mutant cells. Transcriptional induction of the c-Fos target genes collagenase I, stromelysin-1 and stromelysin-2 by UV is almost absent in cells lacking c-fos which correlates with a reduced UV induction of AP-1 DNA-binding and transactivation activity. The repair of UV-induced DNA lesions was not affected, as shown by unscheduled DNA synthesis and host cell reactivation assays. These data demonstrate that c-Fos is involved in a novel protective function other than DNA repair against the harmful consequences of UVC.
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PMID:Fos is an essential component of the mammalian UV response. 748 23

We recently reported that gastrin and glycine-extended progastrin processing intermediates (G-Gly) exert growth-promoting effects on AR4-2J cells (derived from rat pancreas) via interaction with distinct receptors. In this study we sought to investigate the mechanisms by which gastrin and G-Gly stimulate cell proliferation. While gastrin increased [Ca2+]i in AR4-2J cells, G-Gly had no effect. Similarly, G-Gly had no effect either on basal and 10(-7) M vasoactive intestinal polypeptide-stimulated cAMP generation, although gastrin is known to inhibit cAMP generation. Gastrin dose dependently stimulated AR4-2J cell mRNA content of both c-fos and c-jun, two genes known to function in regulating cell proliferation, but G-Gly had no effect. Gastrin also induced the expression of luciferase in AR4-2J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element of the c-fos gene promoter. In similar fashion, gastrin stimulated the activity of mitogen-activated protein kinase, an enzyme known to mediate the induction of the c-fos serum response element in response to growth factor stimulation. Although G-Gly had none of these effects of gastrin in AR4-2J cells, it stimulated activity of c-Jun amino-terminal kinase, an enzyme known to phosphorylate and transcriptionally activate c-Jun. These data support the notion that gastrin stimulates cell proliferation by inducing c-fos and c-jun gene expression, while G-Gly acts by post-translationally regulating early gene transcriptional activation. Our studies represent a novel model in which both the precursor and the product of a key processing reaction, peptide alpha-amidation, act cooperatively to stimulate cell proliferation via distinct receptors linked to different signal transduction pathways.
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PMID:Gastrin and glycine-extended progastrin processing intermediates induce different programs of early gene activation. 749 34

In differentiated 3T3-F442A adipocytes, insulin stimulated rapid and transient phosphorylation of c-Jun. Insulin also stimulated phosphorylation of c-Fos and several Fos-related proteins (pp72, pp45, and pp39) as indicated by precipitation with anti-c-Fos antibody following exposure to denaturating conditions. Phosphorylation of c-Fos was stimulated by 7-fold by 60 min, while phosphorylation of Fos-related proteins reached maxima of 3.5-5.5-fold at 15 to 60 min. The increase in phosphorylated c-Fos was due to an increase in both c-Fos protein and the stoichiometry of c-Fos phosphorylation, and was not observed in c-fos (-/-) cells. Additionally, insulin stimulated phosphorylation of a protein with molecular mass of approximately 82 kDa on tyrosine residues by 2.5-fold within 30 min; this protein appeared to be immunologically related to c-Fos. These increases in the phosphorylation of AP-1 transcription factors correlated with a > 5-fold stimulation of expression of a 12-O-tetradecanoylphorbol-13-acetate-responsive element-chloramphenicol acetyltransferase reporter gene transiently transfected into 3T3-F442A cells. These results indicate that insulin stimulates the phosphorylation of AP-1 transcription factors and several Fos-related proteins on serine and tyrosine residues. This is associated with changes in AP-1-mediated gene expression in vivo, suggesting that AP-1 phosphorylation by insulin plays a role in insulin-regulated gene expression.
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PMID:Insulin stimulates phosphorylation of c-Jun, c-Fos, and Fos-related proteins in cultured adipocytes. 751 56

Liver regeneration factor belongs to the leucine-zipper family of transcription factors. It was originally cloned and characterized through differential screening of a regenerating rat liver cDNA library. The mRNA for liver regeneration factor-1 is barely detectable in normal rat liver but is dramatically induced after two-thirds hepatectomy, with a peak 1 to 3 hr after surgery. The nature of the signaling molecule(s) for this rapid induction is not known. It has been suggested that the liver regeneration factor-1 protein product, through complex interactions with other transcription factors such as c-Jun and Jun-B, controls expression of genes that are required during the G1 phase of hepatic growth. Hepatocyte growth factor has been shown to be the most potent mitogen for hepatocytes in vitro and in vivo. Plasma levels of hepatocyte growth factor rapidly (within 30 min) increase after loss of hepatic parenchyma induced by partial hepatectomy or carbon tetrachloride treatment. It has been postulated that hepatocyte growth factor plays a crucial role in stimulating the hepatocyte to enter the cell cycle. In this communication, we report that addition of pure hepatocyte growth factor to primary cultures of rat hepatocytes in the absence of serum and insulin results in rapid and transient induction of liver regeneration factor-1 mRNA (more than 20-fold) with a peak of expression 1 hr after treatment. The levels of jun-B and c-fos mRNAs, which are also known to be induced during the early hours of liver regeneration, were also increased after treatment of isolated hepatocytes with hepatocyte growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rapid induction of mRNAs for liver regeneration factor and insulin-like growth factor binding protein-1 in primary cultures of rat hepatocytes by hepatocyte growth factor and epidermal growth factor. 752 67

An immunohistochemical study on C-FOS, C-JUN and phosphotyrosine (P-Tyr) cancer gene products was performed. The results showed that C-FOS had the lowest frequency of expression and P-Tyr had the highest. The positive reactions of the three cancer gene products were observed in the nucleus, nuclear membrane and cytoplasm. The expression of C-FOS in normal bronchial and alveolar tissue was 3.8% and 1.6% respectively. But in lung cancer it was 60%. The simultaneous positive expression of C-FOS and C-JUN was 56% (54 cases). Negative C-FOS and positive C-JUN was 32%. Positive C-FOS and negative C-JUN was less than 4% (4 cases). Although C-FOS and C-JUN formed a hetero-dimer by zipper structure, the C-FOS had the ability of single expression.
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PMID:[The expression of C-FOS, C-JUN and phosphotyrosine gene products in lung cancer]. 753 60

Curcumin is a potent inhibitor of tumor promotion, and was shown previously to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity. The c-Fos protein is inducible by TPA and thus is associated with c-Jun to result in an increased AP-1 activity in mouse fibroblast cells. We therefore hypothesized that c-Fos may be one of the targets of curcumin action. In the present study, the effects of curcumin on TPA-induced c-fos mRNA and protein levels were determined by RNA hybridization and western blot analysis, respectively. Curcumin decreases the TPA-induced nuclear abundance of c-Fos protein in spite of the slight super-induction of c-fos mRNA. Upon TPA stimulation, the amount of c-Fos in the quiescent cells increases and reaches maximum at 30 min, and then progressively disappears over a period of 60 min. However, the c-Fos protein seems susceptible to rapid degradation by 45 min if NIH 3T3 cells were treated with TPA in the presence of curcumin. The curcumin-induced hyperphosphorylated forms of c-Fos proteins are significantly more unstable; they entirely disappeared within 40 min after incubation at 37 degrees C. These findings prompted us to suggest that the decrease of c-Fos protein could account for the repressed in vitro DNA binding probably by reducing the Jun/Fos complex formation.
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PMID:A labile hyperphosphorylated c-Fos protein is induced in mouse fibroblast cells treated with a combination of phorbol ester and anti-tumor promoter curcumin. 755 96


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