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)

Steroid receptor coactivator-1 (SRC-1) specifically bound to the transcription factor AP-1 subunits c-Jun and c-Fos, as demonstrated by the yeast two-hybrid tests and glutathione S-transferase pull down assays. The c-Jun and c-Fos binding sites were localized to the C-terminal subregion of SRC-1 (amino acids 1101-1441) that encompasses the previously described histone acetyltransferase and receptor-binding domains. In mammalian cells, SRC-1, similar to the previous results with CBP-p300 (Arias, J., Alberts, A. S., Brindle, P., Claret, F. X., Smeal, T., Karin, M., Feramisco, J., and Montminy, M. (1994) Nature 370, 226-229; Bannister, A. J., and Kouzarides, T. (1995) EMBO J. 14, 4758-4762), potentiated the AP-1-mediated transactivations in a dose-dependent manner and derepressed the mutual inhibitions between nuclear receptors and AP-1. Furthermore, coexpression of p300 further enhanced this SRC-1-potentiated level of transactivations. Thus, we concluded that at least two distinct coactivator molecules may cooperate to regulate AP-1-dependent transactivations and mediate transrepression between AP-1 and nuclear receptors in vivo.
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PMID:Steroid receptor coactivator-1 coactivates activating protein-1-mediated transactivations through interaction with the c-Jun and c-Fos subunits. 964 16

The proto-oncoprotein Bcl-3 is a member of the IkappaB family and is present predominantly in the nucleus. To gain insight into specific nuclear functions of Bcl-3 we have isolated proteins that interact with its ankyrin repeat domain. Using the yeast two-hybrid-system we identified four novel binding partners of Bcl-3 in addition to NF-kappaB p50 and p52, previously known to associate with Bcl-3. The novel Bcl-3 interactors Jab1, Pirin, Tip60 and Bard1 are nuclear proteins which also bind to other transcription factors including c-Jun, nuclear factor I (NFI), HIV-1 Tat or the tumor suppressor and PolII holoenzyme component Brca1, respectively. Bcl-3, p50, and either Bard1, Tip60 or Pirin are sequestered into quarternary complexes on NF-kappaB DNA binding sites, whereas Jab1 enhances p50-Bcl-3-DNA complex formation. Furthermore, the histone acetylase Tip60 enhances Bcl-3-p50 activated transcription through an NF-kappaB binding site, indicating that quarternary complexes containing Bcl-3 interactors modulate NF-kappaB driven gene expression. These data implicate Bcl-3 as an adaptor between NF-kappaB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase.
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PMID:The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators. 1036 52

Transcription factors carry functional domains, which are often physically distinct, for sequence-specific DNA binding, transcriptional activation and regulatory functions. The transcription factor ATF-2 is a DNA-binding protein that binds to cyclic AMP-response elements (CREs), forms a homodimer or heterodimer with c-Jun, and stimulates CRE-dependent transcription. Here we report that ATF-2 is a histone acetyltransferase (HAT), which specifically acetylates histones H2B and H4 in vitro. Motif A, which is located in the HAT domain, is responsible for the stimulation of CRE-dependent transcription; moreover, in response to ultraviolet irradiation, phosphorylation of ATF-2 is accompanied by enhanced HAT activity of ATF-2 and CRE-dependent transcription. These results indicate that phosphorylation of ATF-2 controls its intrinsic HAT activity and its action on CRE-dependent transcription. ATF-2 may represent a new class of sequence-specific factors, which are able to activate transcription by direct effects on chromatin components.
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PMID:ATF-2 has intrinsic histone acetyltransferase activity which is modulated by phosphorylation. 1082 Dec 77

Treatment with retinoic acid (RA) or carnosol, two structurally unrelated compounds with anticancer properties, inhibited phorbol ester (PMA)-mediated induction of activator protein-1 (AP-1) activity and cyclooxygenase-2 (COX-2) expression in human mammary epithelial cells. The induction of COX-2 transcription by PMA was mediated by increased binding of AP-1 to the cyclic AMP response element (CRE) of the COX-2 promoter. Inhibition of the histone acetyltransferase activity of CREB- binding protein (CBP)/p300 blocked the induction of COX-2 by PMA. Treatment with carnosol but not RA blocked increased binding of AP-1 to the COX-2 promoter. Because AP-1 binding was unaffected by RA, we investigated whether RA inhibited COX-2 transcription via effects on the coactivator CBP/p300. Treatment with RA stimulated an interaction between RA receptor-alpha and CBP/p300; a corresponding decrease in the interaction between CBP/p300 and c-Jun was observed. Importantly, overexpressing CBP/p300 or dominant-negative RA receptor-alpha relieved the suppressive effect of RA on PMA-mediated stimulation of the COX-2 promoter. To elucidate the mechanism by which carnosol inhibited COX-2 transcription, its effects on protein kinase C (PKC) signaling were determined. Carnosol but not RA inhibited the activation of PKC, ERK1/2, p38, and c-Jun NH2-terminal kinase mitogen-activated protein kinase. Overexpressing c-Jun but not CBP/p300 reversed the suppressive effect of carnosol on PMA-mediated stimulation of COX-2 promoter activity. Thus, RA acted by a receptor-dependent mechanism to limit the amount of CBP/p300 that was available for AP-1-mediated induction of COX-2. By contrast, carnosol inhibited the induction of COX-2 by blocking PKC signaling and thereby the binding of AP-1 to the CRE of the COX-2 promoter. Taken together, these results show that small molecules can block the activation of COX-2 transcription by distinct mechanisms.
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PMID:Retinoids and carnosol suppress cyclooxygenase-2 transcription by CREB-binding protein/p300-dependent and -independent mechanisms. 1198 Jun 44

Gene expression is coordinated in part by interactions between transcriptional activators and other transcription factors such as coactivators. The KIX domain of the coactivator and histone acetyltransferase CREB binding protein (CBP) binds numerous mammalian and viral transcriptional activators such as BRCA1, CREB, c-Jun, c-Myb, p53, papillomavirus E2, and HTLV-1 Tax. Formation of the CREB-CBP complex depends on phosphorylation of the KID region of CREB and involves induced folding of KID upon binding a hydrophobic groove of the KIX domain of CBP. Here we investigate the formation of the complex formed by human KIX and the N-terminal activation domain of human c-Jun. The c-Jun activation domain and KID do not share significant sequence similarity. Circular dichroism spectroscopy shows that the Jun N-terminal activation domain is intrinsically disordered in isolation and that KIX binding is independent of Jun phosphorylation. In contrast to the mode of binding exhibited by CREB, NMR chemical shift mapping indicates that the c-Jun activation domain binds to a distinctly different surface of KIX than used by CREB. Moreover, NMR and sedimentation equilibrium studies show that the activation domains of c-Jun and CREB can simultaneously bind the KIX domain of CBP. The results illustrate a new mode of binding and combinatorial recruitment via the KIX domain of CBP by multiple transcriptional activators.
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PMID:Structurally distinct modes of recognition of the KIX domain of CBP by Jun and CREB. 1243 52

It is well established that p300 plays an important role in mediating gene expressions. However, it is less clear how its binding is influenced by physiological stimuli and how its altered binding affects transactivator acetylation and binding. In this study, we determined p300 binding to a core cyclooxygenase-2 (COX-2) promoter region by chromatin immunoprecipitation and streptavidin-agarose pull-down assays in basal and tumor necrosis factor-alpha (TNFalpha)-treated human foreskin fibroblasts. We found basal binding of p300, p50/p65 NF-kappaB, cyclic AMP regulatory element-binding protein-2, CCAAT/enhancer-binding protein beta, and c-Jun. p50/p65 and p300 binding was selectively increased by TNFalpha. Immunoprecipitation confirmed direct interaction of p300 with NF-kappaB and the other involved transactivators. p50 acetylation was detected in resting cells and was increased by TNFalpha or lipopolysaccharide. Overexpression of p300 augmented p50 acetylation, which was attenuated by deletion of its histone acetyltransferase domain. Enhanced p50 acetylation correlated with increased p50 binding to COX-2 promoter and transcriptional activation. Co-transfection of E1A with p300 abrogated p50 acetylation and p50 binding. These findings suggest that up-regulation of p300 binding and its acetylation of NF-kappaB occupies a central position in COX-2 promoter activation.
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PMID:Up-regulation of p300 binding and p50 acetylation in tumor necrosis factor-alpha-induced cyclooxygenase-2 promoter activation. 1247 Oct 36

Gene activation in eukaryotes requires chromatin remodeling, in part via histone modifications. To study the events at the promoter of a mitogen-inducible gene, we examined the induction of expression of the collagenase gene. It has been established that the collagenase gene can be activated by c-Jun and c-Fos and that the transcriptional coactivator p300 is involved in the activation. As expected, we found histone acetyltransferase activity at the collagenase promoter during activation. Interestingly, we also found histone methyltransferase and kinase activity. Strikingly, the first modification observed is methylation of histone H3 lysine 4, which correlates with the binding of the SET9 methyltransferase and the assembly of a complex consisting of c-Jun, c-Fos, TATA binding protein, and RNA polymerase II. The assembly of the preinitiation complex also shows an ordered binding of the acetyltransferase p300, the RSK2 kinase, and the SWI/SNF component Brg-1. Our results suggest that collagenase gene activation involves a dynamic recruitment of different factors and that in addition to acetylation, histone H3 lysine 4 di- and trimethylation and histone H3 serine 10 phosphorylation are important steps in the activation of this gene.
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PMID:Cascade of distinct histone modifications during collagenase gene activation. 1258 98

p300 and cAMP response element binding protein (CREB)-binding protein (CBP) are two highly homologous, conserved transcriptional coactivators, and histone acetyltransferases (HATs) that link chromatin remodeling with transcription. Cell transformation by viral oncogene products such as adenovirus E1A and SV40 large T antigen depends on their ability to inactivate p300 and CBP. To investigate the role of p300 in cell-cycle progression, we constructed stable rat cell lines, which conditionally overexpress p300 from a tetracycline-responsive promoter. When p300 was induced in these cells, serum-stimulated S-phase entry was significantly inhibited. The inhibition of S-phase induction was associated with down-regulation of c-Myc, but not of c-Fos or c-Jun. Simultaneous overexpression of c-Myc and p300 before serum stimulation reversed the inhibition of S-phase induction to a significant level, indicating that the inhibition of c-Myc to a large extent is responsible for the p300 inhibition of G1 exit. Similar studies with stable rat cell lines that overexpress a mutant p300, which lacks the HAT activity, showed that the intrinsic HAT activity of p300 is not required for the negative regulation of c-Myc or G1. These findings, and our previously published results (Kolli, S., Buchmann, A. M., Williams, J., Weitzman, S. & Thimmapaya, B. (2001) Proc. Natl. Acad. Sci. USA 98, 4646-4651), establish an important negative regulatory role for p300 in c-Myc expression that may be important in maintaining the cells in the G0/G1 phase of the cell cycle.
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PMID:Repression of c-Myc and inhibition of G1 exit in cells conditionally overexpressing p300 that is not dependent on its histone acetyltransferase activity. 1288 11

Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein localized specifically in the mineralized matrix of bone and dentin. Expression analyses demonstrate that DMP1 is differentially regulated in osteoblasts and odontoblasts. Earlier we have reported on the transcriptional regulation of DMP1 by c-Fos and c-Jun (AP-1) transcription factors. Results from earlier study indicate that c-Fos and c-Jun play an important role in early osteoblast differentiation, whereas they do not have a significant effect on the terminally differentiated osteoblasts. In this paper, we demonstrate a regulatory mechanism by which JunB transcriptionally controls the expression of DMP1 during osteoblast differentiation. The cooperative interaction of JunB with p300 has been shown to dramatically modulate the DMP1 promoter activity during mineralization. Immunoprecipitation and chromatin immunoprecipitation analysis demonstrate the interaction of JunB and p300 in vivo. Further, phosphorylation of JunB at Ser-79 was found to be essential for its interaction with p300. Intrinsic histone acetyltransferase activity of p300 also plays a critical role in regulating DMP1 gene expression.
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PMID:Transcriptional regulation of dentin matrix protein 1 by JunB and p300 during osteoblast differentiation. 1530 41

In human immunodeficiency virus type 1 (HIV-1)-infected cells, a cell cycle arrest in G(2) increases viral expression and may represent a strategy for the virus to optimize its expression. In latently infected cells, balance between viral silencing and reactivation relies on the nucleosomal organization of the integrated long terminal repeat (LTR). It is shown here that nucleosome nuc-1, which is located downstream of the TATA box, is specifically modified when latently infected cells are arrested in G(2) by chemical inducers. Notably, histones H3 and H4 are hyperacetylated, and this modification is associated with an increased LTR-driven transcription. nuc-1 hyperacetylation is also associated with the recruitment of histone acetyltransferase CBP and transcription factors NF-kappaB and c-Jun. NF-kappaB and/or c-Jun binding to the LTR in G(2)-arrested cells appears to be required for CBP recruitment as well as for nuc-1 remodeling and viral reactivation.
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PMID:Cell cycle arrest in G2 induces human immunodeficiency virus type 1 transcriptional activation through histone acetylation and recruitment of CBP, NF-kappaB, and c-Jun to the long terminal repeat promoter. 1550 6


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