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

Transcription factor AP-1 is inducible by phorbol esters and thus could be considered to be one final target of the protein kinase C signal transduction pathway. AP-1 consists of the products of the fos and jun oncogenes, which associate as dimers to bind TPA-responsive promoter elements (TRE) efficiently. We show that AP-1 activity is modulated by an inhibitory protein (IP-1), present both in the nucleus and cytoplasm of several cell types. IP-1 specifically blocks DNA binding of AP-1 from nuclear extracts and of in vitro synthesized Fos/Jun proteins. It is a labile protein of 30-40 kd, which exerts its activity only in the nonphosphorylated form. Block of IP-1 function is obtained by PKA-mediated phosphorylation, possibly suggesting a cross talk mechanism at transcriptional level. Competition experiments with synthetic peptides suggest that IP-1 could interact with Fos and/or Jun leucine zippers. We speculate that IP-1 might act as a transcriptional antioncogene.
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PMID:IP-1: a dominant inhibitor of Fos/Jun whose activity is modulated by phosphorylation. 190 Apr 58

Liver regeneration provides one of the few systems for analysis of mitogenesis in the fully developed, intact animal. Several proteins have been identified as part of the primary growth response in regenerating liver and in mitogen-stimulated cells. Some of these proteins, such as the Jun and Fos families of transcription factors, are thought to have a role in activating transcription of genes expressed subsequently in the growth response. Through differential screening of a regenerating-liver cDNA library, we have identified a rapidly and highly induced gene encoding a 21-kDa leucine-zipper-containing protein that we have designated liver regeneration factor 1 (LRF-1). LRF-1 has no homology with other leucine-zipper proteins outside the basic and leucine-zipper domains. LRF-1 alone can bind DNA, but it preferentially forms heteromeric complexes with c-Jun and Jun-B and does not interact with c-Fos. In solution, it binds with highest affinity to cAMP response elements but also has affinity for related sites. In cotransfection studies, LRF-1 in combination with c-Jun strongly activates a c-Jun-responsive promoter. The induction of the LRF-1 gene in regenerating liver greatly increases the potential variety of heterodimeric combinations of leucine-zipper transcription factors. While LRF-1 mRNA is rapidly induced in the absence of protein synthesis, its peak induction is later than c-fos mRNA, suggesting that LRF-1 may regulate responsive genes at a later point in the cell cycle. As such, LRF-1 may have a unique and critical role in growth regulation of regenerating liver and mitogen-stimulated cells.
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PMID:Identification of LRF-1, a leucine-zipper protein that is rapidly and highly induced in regenerating liver. 190 65

We present evidence that oestrogen receptor activity in human MCF-7 breast cancer cells is reduced by over-expression of c-Jun or c-Fos proteins and to a lesser extent by Jun B overexpression. In contrast, overexpression of Jun D protein does not affect the activity of the oestrogen receptor. A region of c-Jun found to be required for repression of oestrogen receptor activity is located outside the DNA binding domain and is not conserved among the three Jun proteins. Finally, we suggest that c-Jun and c-Fos act independently to inactivate the oestrogen receptor.
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PMID:Unregulated expression of c-Jun or c-Fos proteins but not Jun D inhibits oestrogen receptor activity in human breast cancer derived cells. 190 1

The AP-1 family of transcription factors, which includes the proto-oncogene products c-Jun and c-Fos, controls the stimulation of cellular genes by growth factors and the expression of oncogenes, including src and ras. Transcriptional activation by c-Jun is regulated by a cell-type-specific inhibitor that represses the activity of a transcriptional activation domain (A1) of c-Jun by operating through the adjacent negative regulatory region (delta). Here we show that cotransfection of the src or ras oncogene enhances the transcriptional activity of a GAL4:c-Jun hybrid that includes the delta-A1 region of c-Jun, suggesting that the DNA binding and dimerization domain of c-Jun is not required for stimulation by Src or Ras. Moreover, induction of c-Jun activity by Src and Ras occurs in cell lines containing the c-Jun inhibitor but not in a cell line lacking it. The region in c-Jun essential for the stimulatory action of these oncogenes maps to domain A1. These findings suggest the existence of signal-transduction pathways that result in an increase in transcriptional activity of c-Jun and AP-1 by disrupting the c-Jun:inhibitor interaction.
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PMID:v-Src and EJ Ras alleviate repression of c-Jun by a cell-specific inhibitor. 190 40

The expression of different members of the Jun and Fos families of transcription factors is rapidly induced following serum stimulation of quiescent fibroblasts. To determine whether these proteins are required for cell cycle progression, we microinjected affinity-purified antibodies directed against c-Fos, FosB, Fra-1, c-Jun, JunB, and JunD, and antibodies that recognize either the Fos or the Jun family of proteins, into Swiss 3T3 cells and determined their effects in cell cycle progression by monitoring DNA synthesis. We found that microinjection of anti-Fos and anti-Jun family antibodies efficiently blocked the entrance to the S phase of serum-stimulated or asynchronously growing cells. However, the antibodies against single members of the Fos family only partially inhibited DNA synthesis. In contrast, all three Jun antibodies prevented DNA synthesis more effectively than did any of the anti-Fos antibodies.
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PMID:The jun and fos protein families are both required for cell cycle progression in fibroblasts. 190 53

c-Jun protein, and AP1/PEA1 transcription factor component, is a typical short-lived protein, and like other short-lived proteins such as c-Fos, contains PEST regions. Calcium-dependent neutral protease (calpain), a candidate for the degradation of PEST-containing proteins, digests c-Jun and c-Fos efficiently in vitro. This is the first demonstration that transcription factors are substrates for calpain. The C-terminal portion of c-Jun is relatively resistant to calpain such that an 18kDa fragment, which includes the DNA binding domain, accumulates under moderate digestion conditions. The activity of c-Jun in cultured cells can be modified by changing the level of calpastatin, an endogenous calpain inhibitor, indicating that c-Jun is also a substrate for calpain in vivo.
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PMID:Degradation of transcription factors, c-Jun and c-Fos, by calpain. 190 91

We have isolated and characterized the chicken junD gene. It does not contain an intron; its upstream regulatory sequences lack the AP-1-binding site seen in c-jun but include two CRE elements. Downstream untranslated sequences do not show the destabilizing signal ATTTA. The amino acid sequence of the chicken JunD protein is closely related to that of mouse JunD in the dimerization and DNA contact surfaces of the carboxy-terminal region; additional homologies to mouse JunD are seen in acidic and amphipathic amino-terminal domains. Chicken JunD contains stretches of oligoglycines, alanines and prolines, possibly acting as hinges that connect functionally distinct domains of the protein. Chicken junD is broadly expressed at low basal levels in differentiated tissues and at somewhat higher levels in cultured fibroblasts. The cDNA clone of junD was transcribed and translated in vitro. The resulting JunD protein migrates in between 40 and 50 kDa in an SDS gel and can be precipitated with an antibody prepared against a polypeptide consisting of the carboxy-terminal 100 amino acids of mouse c-Jun.
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PMID:The chicken junD gene and its product. 192 29

The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth.
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PMID:Overexpression of c-jun, junB, or junD affects cell growth differently. 192 49

An intragenic enhancer in the pol gene of human immunodeficiency virus type 1 has previously been identified (Verdin et al., Proc. Natl. Acad. Sci. USA 87:4874-4878, 1990). This element is composed of two subdomains both exhibiting phorbol ester-inducible enhancing activity on the viral thymidine kinase promoter in HeLa cells. Examination of the nucleotide sequence of one of these domains (nucleotides 4079 to 4342, HXB2 isolate) revealed the presence of three short DNA regions highly homologous to the recognition site for cellular transcription factor AP-1. Two short oligonucleotides containing these AP-1 sites each functioned as a phorbol ester-inducible enhancer when cloned upstream of the thymidine kinase promoter and transfected into HeLa cells. Gel mobility shift assays and competition experiments using the same two oligonucleotides demonstrated that they bound affinity-purified AP-1 or AP-1 present in uninduced and 12-O-tetradecanoylphorbol-13-acetate-induced HeLa nuclear extracts. Footprinting experiments confirmed that all three predicted sites bound purified AP-1. These results suggest that the AP-1 factor could play a role in the transcriptional regulation of human immunodeficiency virus type 1 gene expression.
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PMID:The intragenic enhancer of human immunodeficiency virus type 1 contains functional AP-1 binding sites. 194 59

Many essential biological pathways, including cell growth, development, and metabolism, are regulated by thyroid hormones (THs). TH action is mediated by intracellular receptors that belong to a large family of ligand-dependent transcription factors, including the steroid hormone and retinoic acid receptors. So far it has been assumed that TH receptors (TRs) regulate gene transcription only through the classical protein-DNA interaction mechanism. Here we provide evidence for a regulatory pathway that allows cross-talk between TRs and the signal transduction pathway used by many growth factors, oncogenes, and tumor promoters. In transient transfection studies, we observed that the oncogenes c-jun and c-fos inhibit TR activities, while TRs inhibit induction of the c-fos promoter and repress AP-1 site-dependent gene activation. A truncated TR that lacks only 17 amino acids from the carboxy terminus can no longer antagonize AP-1 activity. The cross-regulation between TRs and the signal transduction pathway appears to be based on the ability of TRs to inhibit DNA binding of the transcription factor AP-1 in the presence of THs. The constituents of AP-1, c-Jun, and c-Fos, vice versa, can inhibit TR-induced gene activation in vivo, and c-Jun inhibits TR DNA binding in vitro. This novel regulatory pathway is likely to play a major role in growth control and differentiation by THs.
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PMID:Novel pathway for thyroid hormone receptor action through interaction with jun and fos oncogene activities. 194 74


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