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

We have characterized a transcriptional enhancer of the human urokinase-type plasminogen activator (uPA) gene in three transformed human cell lines: HeLa, HepG2 and HT1080. The enhancer is located approximately 2 kbp upstream of the mRNA cap site and is active in all three cell lines. By footprinting and gel retardation analysis we found that it contained two binding sites for transcription factor AP-1, encoded by the fos and jun proto-oncogene families. The most upstream of these sites was juxtaposed to a binding site for PEA3, a product of the ets/Spi proto-oncogene family. By transient transfection analysis of deletions, point mutations and subcloned fragments, we found these sites to be crucial for enhancer activity. However, the sites displayed differences in activity in the three different cell lines. The downstream AP-1 site was almost exclusively responsible for enhancer activity in HeLa cells, whereas the AP-1/PEA3 site played a major role in HT1080 and HepG2 cells. The implications of our findings for the known regulation of uPA expression by transforming oncogenes, adenovirus E1A protein and glucocorticoids are discussed.
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PMID:Essential AP-1 and PEA3 binding elements in the human urokinase enhancer display cell type-specific activity. 192 25

The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo cells in cooperation with an activated c-Ha-ras gene. By deletion analysis, we identified the regions of c-Jun encoding transformation and transactivation functions. Our studies indicate that there is a direct correlation between the ability of the c-Jun protein to activate transcription and cotransform rat embryo cells. The regions involved in these functions include the conserved leucine zipper/DNA binding domain and an effector domain near its N terminus. This N-terminal region spans amino acids 61 to 146 of the c-Jun protein and is highly conserved among all Jun family members. These results support the hypothesis that c-Jun transforms cells by stimulating the expression of transformation-mediating genes.
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PMID:The transactivating domain of the c-Jun proto-oncoprotein is required for cotransformation of rat embryo cells. 194 89

The mammalian transcription factor AP-2 is a retinoic acid inducible sequence-specific DNA-binding protein that is developmentally regulated. In this report, the functional domains necessary for AP-2 DNA binding were studied. AP-2 required a dimerization domain and an adjacent region of net basic charge to achieve a sequence-specific protein:DNA interaction. The sequences responsible for dimerization consisted of two putative amphipathic alpha helices separated by a large intervening span region. This helix-span-helix (HSH) domain was unable to bind DNA when separated from the basic region, but was still capable of dimerization. The ability of the HSH domain to function as a module that promotes DNA binding through dimerization was further demonstrated by attaching it to the heterologous basic region of the c-Jun proto-oncogene product. The resulting chimeric protein specifically recognized an AP-1 DNA-binding site in the absence of an intact c-Jun leucine repeat and in a manner that was dependent on the presence of a functional AP-2 dimerization domain.
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PMID:Characterization of a dimerization motif in AP-2 and its function in heterologous DNA-binding proteins. 199 22

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

The product of the jun proto-oncogene has been identified as one form of the transcription factor AP-1. The p55fos protein associates with jun/AP-1 by means of a heterodimer which requires intact 'leucine zipper' domains of both proteins. The fos/jun heterodimer binds to and activates transcription from TPA-responsive promoter elements (TGACTCA), which represent one final target of the protein kinase C pathway. The other main signal transduction pathway, initiated by the activation of the adenylate cyclase, involves the transcription factor CREB. The promoter element recognized by CREB, a cyclic AMP responsive element (CRE), consist of a palyndromic sequence similar to a TRE (TGACGTCA). We show that jun efficiently trans-activates CRE sequences and that fos and jun efficiently bind and cooperate in activating CRE promoter elements. The similarity between TRE and CRE sequences may involve an interplay in transcriptional regulation and 'cross-talk' between components of the two major signal transduction pathways.
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PMID:Cross-talk in signal transduction: TPA-inducible factor jun/AP-1 activates cAMP-responsive enhancer elements. 210 94

To assess the transforming capability of the c-Jun protein, we introduced the chicken c-jun proto-oncogene into a replication competent avian retroviral expression vector (RCAS). Viral Jun efficiently transformed chicken embryo fibroblasts (CEFs) when expressed from this vector. Overexpression of c-Jun leads to transformation of CEFs with an efficiency that is 15- to 25-fold less than that seen for v-Jun, suggesting that v-Jun contains structural features that increase its oncogenic potential relative to c-Jun. There are four structural differences between v-Jun and c-Jun. To determine the relative contribution that each of these structural differences between v-Jun and c-Jun has on oncogenic activity, several deletion and substitution mutants were constructed. Each of these mutants was expressed in CEF and assayed for transformation by focus formation. Analysis of the results reveals that deletion of a region of 27 amino acids near the amino terminus of c-Jun and deletion of 3'-untranslated sequences are critical in activating the full oncogenic potential of Jun.
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PMID:Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences. 212 64

Cellular and viral Fos proteins form a tight complex with other nuclear proteins, including the transcription factor and proto-oncogene AP-1/Jun. We have mapped the c-Jun binding site in Fos to a region containing regularly spaced leucine residues recently suggested to interdigitate with a similar structure in Jun. Substitution of single or multiple leucine residues or the alteration of leucine phasing by insertion of additional amino acids reduces or abolishes the binding to Jun, while the substitution of other amino acids has no noticeable effect. These results strongly suggest that the formation of a "leucine zipper" mediates the interaction between Fos and Jun. We also show that the differential binding of the various Fos mutants correlates with their potential to trans-activate AP-1-dependent transcription and to induce morphological transformation.
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PMID:The leucine repeat motif in Fos protein mediates complex formation with Jun/AP-1 and is required for transformation. 249 53

The human proto-oncogene product, c-Jun, is a member of the AP-1 family of transcription factors, which mediate the regulation of gene expression in response to extracellular signaling. Comparison of c-Jun and v-Jun by in vitro transcription assays revealed that v-Jun has significantly greater transcriptional activity than c-Jun. Analysis of Jun mutants expressed in bacteria indicates that this difference in transcriptional activity is due to the presence of a regulatory domain located at the N-terminal region of c-Jun. Other Jun mutants identify an activation domain rich in acidic and proline residues toward the C-terminal end of the molecule, in a region near the DNA binding domain. These findings suggest that during retroviral transduction, a constitutively active Jun protein has been generated by deleting a negatively acting domain. This putative repressor domain may also play a role in the signal-dependent induction of c-Jun activity.
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PMID:Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. 251 Sep 34

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

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


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