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

The origins of DNA replication (ori) in simian virus 40 (SV40) and polyomavirus (Py) contain an auxiliary component (aux-2) composed of multiple transcription factor binding sites. To determine whether this component stimulated replication by binding specific transcription factors, aux-2 was replaced by synthetic oligonucleotides that bound a single transcription factor. Sp1 and T-antigen (T-ag) sites, which exist in the natural SV40 aux-2 sequence, provided approximately 75 and approximately 20%, respectively, of aux-2 activity when transfected into monkey cells. In cell extracts, only T-ag sites were active. AP1 binding sites could replace completely either SV40 or Py aux-2. Mutations that eliminated AP1 binding also eliminated AP1 stimulation of replication. Yeast GAL4 binding sites that strongly stimulated transcription in the presence of GAL4 proteins failed to stimulate SV40 DNA replication, although they did partially replace Py aux-2. Stimulation required the presence of proteins consisting of the GAL4 DNA binding domain fused to specific activation domains such as VP16 or c-Jun. These data demonstrate a clear role for transcription factors with specific activation domains in activating both SV40 and Py ori. However, no correlation was observed between the ability of specific proteins to stimulate promoter activity and their ability to stimulate origin activity. We propose that only transcription factors whose specific activation domains can interact with the T-ag initiation complex can stimulate SV40 and Py ori-core activity.
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PMID:Specific transcription factors stimulate simian virus 40 and polyomavirus origins of DNA replication. 131 5

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.
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PMID:The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1. 140 31

Transcription of tissue inhibitor of metalloproteinases-1 (TIMP-1), a secreted protein that regulates the activities of the metalloproteinases, collagenase and stromelysin, is activated by serum growth factors. Transient transfection experiments have revealed several regions of cis-acting regulatory sequences involved in the response of the murine TIMP-1 gene to serum. One area is in the vicinity of the promoter, consisting of a non-consensus binding site (5'-TGAGTAA-3' at -59/-53) for transcription factor AP1 and an adjacent 24 bp region of dyad symmetry that contains a PEA3-binding site. A second is an upstream region (-1020 to -780) that acts as an enhancer when linked to a heterologous promoter, and contains a consensus AP1 binding site (at -803/ -797). Gel retardation assays revealed differences between nuclear factors in mouse C3H10T1/2 cells that bound to the TIMP(-59/ -53)AP1 site and a consensus collagenase TRE (TPA-response element). The TIMP(-59/ -53)AP1 site is a promiscuous motif that binds c-Fos/c-Jun AP1 translated in vitro and is an effective competitor for binding of nuclear AP1 factors to the consensus TRE, but in addition it binds factors that do not associate with the consensus TRE. The TIMP(-59/ -53)AP1 motif and the dyad symmetry region stimulated expression from a thymidine kinase promoter in an additive fashion, and competition experiments showed that excess copies of these factor binding sites reduced expression from a reporter plasmid driven by the TIMP-1 promoter. Our data show that binding sites for AP1 and PEA3 transcription factors are involved in the regulation of TIMP-1 transcription, which suggests that the coordinated induction of TIMP-1, collagenase and stromelysin may be achieved through the actions of a shared set of nuclear transcription factors. However, the properties of the TIMP-1(-59/ -53)AP1 motif likely reflect an additional type of transcriptional regulation restricted to TIMP-1.
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PMID:Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases-1 (TIMP-1) transcription. 142 Mar 63

The ability of the c-Jun protein, the main component of the transcription factor AP1, to interact directly or indirectly with the RNA polymerase II-initiation complex to activate transcription was investigated by in vivo transcription interference ("squelching") experiments. Coexpression of a Jun mutant lacking its DNA binding domain strongly represses the activity of wild-type c-Jun. Repression depends on the presence of the transactivation domains (TADs), suggesting that a limiting factor interacting with the TADs is essential to link Jun and the components of the transcriptional machinery. The activity of this intermediary factor(s) is restricted to TADs characterized by an abundance of negatively charged amino acids, as demonstrated by the abilities of the TADs of JunB, GAL4, and VP16 to repress c-Jun activity. Depending on the presence of the TADs of Jun, we found physical interaction between Jun and a cluster of three proteins with molecular masses of 52, 53, and 54 kDa (p52/54). Association between Jun and p52/54 is strongly reduced in the presence of VP16, suggesting that the two proteins compete for binding to p52/54. Transcription factors containing a different type of TAD (e.g., GHF1, estrogen receptor, or serum response factor) fail to inhibit Jun activity, suggesting that these proteins act through a different mechanism. We consider the requirement of Jun to interact with p52/54 utilized by other transcription factors a new mechanism in the regulation of transcription of Jun-dependent target genes.
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PMID:A common intermediary factor (p52/54) recognizing "acidic blob"-type domains is required for transcriptional activation by the Jun proteins. 144 82

The ets-1 proto-oncogene codes for a transcription factor. In order to understand how ets-1 is regulated, we have cloned its promoter. We show that the promoter is inducible by serum and expression of c-Fos and c-Jun, and it is positively auto-regulated by its gene product. A 50 base-pair sequence is sufficient to confer c-Fos + c-Jun and c-Ets-1 responsiveness to a heterologous promoter. This element contains two AP1 and one Ets-1 like motifs. Striking, AP-1 and Ets-1 motifs are found in oncogene responsive units (ORU's) of other promoters, suggesting that combining these motifs is a common mechanism for generating mitogen responsive transcription elements.
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PMID:Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. 161 56

A panel of epitope-specific antibodies, directed against c-Fos, c-Jun, and FosB derived oligopeptide sequences, was generated and used to study the interaction of Fos and Jun proteins and the binding of the Fos/Jun complex to the AP1-binding site (TRE). Our results strongly support results previously obtained by site-directed mutagenesis experiments. The leucine zipper is the major site of interaction between Fos and Jun. Antibodies directed against this domain of Fos bound free Fos protein efficiently, but were unable to recognize Fos within the Fos/Jun complex. In contrast, all other Fos epitope-specific antibodies showed similar reactivity with both free and complexed Fos. Antibodies directed against sequences adjacent to the leucine zipper inhibited formation of the complex. This may suggest that amino acids in the vicinity of the leucine zipper may also play some role in the formation of the protein complex. Binding of Fos/Jun to the TRE was inhibited only by antibodies directed against the basic regions in Fos or Jun previously suggested to represent the DNA binding sites. The fact that very similar results were obtained by two totally different strategies, i.e., mutagenesis experiments and domain mapping using epitope-specific antibodies, lends strong support to the proposed domain structure of Fos and Jun family members.
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PMID:Mapping of functional domains in Fos and Jun proteins using epitope-specific antibodies. 169 78

Polyomavirus (Py) DNA replication is regulated by its enhancer, which contains an AP1 site, c-Jun and c-Fos, the products of nuclear protooncogenes c-jun and c-fos, form the heterodimeric transcriptional activating factor AP1. Overexpression of c-fos and c-jun genes strongly stimulated Py DNA replication from the Py origin of replication as well as transcription from the Py early promoter through the AP1 binding site. The cAMP response element (CRE)-binding protein CREB stimulated only transcription, not DNA replication, through the CRE under similar conditions. The results indicate that AP1 functions as a regulator of DNA replication and that the mechanism of activation of Py DNA replication by AP1 is distinct from that of activation of transcription from the Py early promoter.
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PMID:The nuclear protooncogenes c-jun and c-fos as regulators of DNA replication. 185 Aug 42

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

The regulation of jun family genes and AP1 activity during the course of differentiation of F9 embryonal carcinoma stem cells was investigated. The induction of differentiation by retinoic acid (RA) leads to an accumulation of c-jun mRNA caused by increased c-jun transcription. This induction is an indirect response to RA and requires a functional AP1 binding site within the c-jun promoter. Expression of jun-B mRNA, however, is transiently induced but at a later time point is repressed by RA. The third member of the family, jun-D, is already active in undifferentiated cells and is only slightly induced after differentiation. Differentiation also converts c-jun from being refractory to phorbol esters to a highly inducible state. The development of this response is correlated with increased AP1 activity in RA-treated cells. By contrast, the induction of c-fos by phorbol esters or cAMP is greatly diminished after RA treatment. Transfection experiments indicate that, in the absence of c-Fos, only c-Jun is an effective transactivator. Hence, the major increase in AP1 activity is due to elevated c-jun expression and probably involves positive autoregulation by the c-Jun protein. Furthermore, these results demonstrate that AP1 activity can be stimulated by phorbol ester without concomitant c-fos induction. Forced expression of c-Jun and v-Jun results in activation of at least two differentiation marker genes, EndoB and tissue plasminogen activator, whose regulatory regions contain AP1 binding sites. Thus, the induction of c-jun transcription by RA, although indirect, can have an important role in the differentiation process.
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PMID:Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. 196 81

The coding sequences of avian (quail) or murine c-jun proto-oncogenes were introduced into a non-defective retroviral vector derived from Rous sarcoma virus (RSV) in which c-jun replaces v-src. Primary avian fibroblasts chronically infected with either one of these viruses exhibit some phenotypic traits characteristic of RSV-transformed cells, including sustained growth in low serum medium and ability to develop colonies from single cells in agar, even though they are still of normal morphology and contact inhibited. This altered growth control correlates with enhanced AP1-specific DNA binding activity as well as with higher levels of c-Jun products. Unexpectedly, repression of the endogenous c-Jun product is observed in cells overexpressing murine c-Jun. Cells expressing the avian and the murine c-Jun products display qualitatively similar phenotypes; nevertheless, for every transformed trait considered, the murine c-jun seemed more potent than its quail homologue. These data suggest that the avian or murine c-jun proto-oncogenes may trigger a subset of the 'transforming functions' normally induced by v-src, and which are more specifically related to growth in low serum and in the absence of solid support.
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PMID:Overexpression of avian or mouse c-jun in primary chick embryo fibroblasts confers a partially transformed phenotype. 212 32


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