Genomes and Genes
p300 cbp transcription factors
Summary: A family of histone acetyltransferases that is structurally-related to CREB-BINDING PROTEIN and to E1A-ASSOCIATED P300 PROTEIN. They function as transcriptional coactivators by bridging between DNA-binding TRANSCRIPTION FACTORS and the basal transcription machinery. They also modify transcription factors and CHROMATIN through ACETYLATION.
- Karmakar S, Mahajan M, Schulz V, Boyapaty G, Weissman S. A multiprotein complex necessary for both transcription and DNA replication at the ?-globin locus. EMBO J. 2010;29:3260-71 pubmed publisher..These results imply a direct link between mammalian DNA replication, transcription and histone acetylation mediated by a single multiprotein complex. ..
- Morimoto T, Sunagawa Y, Fujita M, Hasegawa K. Novel heart failure therapy targeting transcriptional pathway in cardiomyocytes by a natural compound, curcumin. Circ J. 2010;74:1059-66 pubmed..Curcumin inhibits p300-mediated nuclear acetylation, suggesting its usefulness in HF treatment. Clinical application of this natural compound, which is inexpensive and safe, should be established in the near future. ..
- Salem M, Shalbaf M, Gibbons N, Chavan B, Thornton J, Schallreuter K. Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage. FASEB J. 2009;23:3790-807 pubmed publisher..Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo. ..
- D Orso I, Frankel A. Tat acetylation modulates assembly of a viral-host RNA-protein transcription complex. Proc Natl Acad Sci U S A. 2009;106:3101-6 pubmed publisher..Thus, lysine acetylation can be used to modulate and evolve the strength of a viral-host RNA-protein complex, thereby tuning the levels of transcription elongation...
- Tan H, Porter A. p21(WAF1) negatively regulates DNMT1 expression in mammalian cells. Biochem Biophys Res Commun. 2009;382:171-6 pubmed publisher..This novel p21(WAF1)-p300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division. ..
- Chew J, Biswas S, Shreeram S, Humaidi M, Wong E, Dhillion M, et al. WIP1 phosphatase is a negative regulator of NF-kappaB signalling. Nat Cell Biol. 2009;11:659-66 pubmed publisher..Consistent with our results, mice lacking WIP1 showed enhanced inflammation. These results provide the first genetic proof that a phosphatase directly regulates NF-kappaB signalling in vivo. ..
- Yoshioka T, Inagaki K, Noguchi T, Sakai M, Ogawa W, Hosooka T, et al. Identification and characterization of an alternative promoter of the human PGC-1alpha gene. Biochem Biophys Res Commun. 2009;381:537-43 pubmed publisher..Our results thus reveal a potential molecular basis for isoform-specific regulation of PGC-1alpha expression in contracting muscle. ..
- Ropelle E, Pauli J, Prada P, Cintra D, Rocha G, Moraes J, et al. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats. J Physiol. 2009;587:2341-51 pubmed publisher..Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity. ..
- Lucki N, Sewer M. The cAMP-responsive element binding protein (CREB) regulates the expression of acid ceramidase (ASAH1) in H295R human adrenocortical cells. Biochim Biophys Acta. 2009;1791:706-13 pubmed publisher..These data identify the ACTH/cAMP signaling pathway and CREB as transcriptional regulators of the ASAH1 gene in the human adrenal cortex. ..
- Pradeepa M, Nikhil G, Hari Kishore A, Bharath G, Kundu T, Rao M. Acetylation of transition protein 2 (TP2) by KAT3B (p300) alters its DNA condensation property and interaction with putative histone chaperone NPM3. J Biol Chem. 2009;284:29956-67 pubmed publisher..Interestingly, acetylation of TP2 impedes its interaction with NPM3. Thus, acetylation of TP2 adds a new dimension to its role in the dynamic reorganization of chromatin during mammalian spermiogenesis. ..
- Dekker F, Haisma H. Histone acetyl transferases as emerging drug targets. Drug Discov Today. 2009;14:942-8 pubmed publisher..This review focuses on the role of the HATs p300, CBP, PCAF and GCN5 in different diseases and the development of small-molecule inhibitors of these enzymes as potential drugs. ..
- Gao X, Pan W, Dai H, Zhang Y, Wu N, Shen Y. CARM1 activates myogenin gene via PCAF in the early differentiation of TPA-induced rhabdomyosarcoma-derived cells. J Cell Biochem. 2010;110:162-70 pubmed publisher..The findings shed lights on novel therapeutic targets in the treatment of rhabdomyosarcoma patients. ..
- Ortiz Ortiz M, Moran J, Ruiz Mesa L, Bravo San Pedro J, Fuentes J. Paraquat exposure induces nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the activation of the nitric oxide-GAPDH-Siah cell death cascade. Toxicol Sci. 2010;116:614-22 pubmed publisher..The results suggest that PQ induces this novel cell death cascade in rat mesencephalic cells, but inhibition of the pathway does not impede cell death because of an oxidative burst generated by the pesticide. ..
- Xiong S, Salazar G, San Martin A, Ahmad M, Patrushev N, Hilenski L, et al. PGC-1 alpha serine 570 phosphorylation and GCN5-mediated acetylation by angiotensin II drive catalase down-regulation and vascular hypertrophy. J Biol Chem. 2010;285:2474-87 pubmed publisher..We provide novel mechanistic insights by which Ang II may mediate its ROS-dependent pathophysiologic effects on multiple cardiometabolic diseases. ..
- Liu Z, Mai A, Sun J. Lysine acetylation regulates Bruton's tyrosine kinase in B cell activation. J Immunol. 2010;184:244-54 pubmed publisher..Together, our results indicate a novel regulatory mechanism for Btk transcription and reveal a previously unrecognized posttranslational modification of the Btk protein and its association with phosphorylation in B cell activation. ..
- Nakagawa Y, Kuwahara K, Takemura G, Akao M, Kato M, Arai Y, et al. p300 plays a critical role in maintaining cardiac mitochondrial function and cell survival in postnatal hearts. Circ Res. 2009;105:746-54 pubmed publisher..Collectively, our findings suggest that p300 is essential for the maintenance of mitochondrial integrity and for myocyte survival in the postnatal left ventricular myocardium. ..
- Gillespie R, Gudas L. Retinoid regulated association of transcriptional co-regulators and the polycomb group protein SUZ12 with the retinoic acid response elements of Hoxa1, RARbeta(2), and Cyp26A1 in F9 embryonal carcinoma cells. J Mol Biol. 2007;372:298-316 pubmed..These studies provide insight into the dynamics of association of co-regulators with RAREs and demonstrate a novel link between RA signaling and PcG repression. ..
- Rodriguez Navarro S. Insights into SAGA function during gene expression. EMBO Rep. 2009;10:843-50 pubmed publisher..I focus particularly on the new components of human SAGA, which was recently discovered and confirms the conservation of the SAGA complex throughout evolution. ..
- Tu S, Chi A, Ai W, Takaishi S, Dubeykovskaya Z, Quante M, et al. p53 inhibition of AP1-dependent TFF2 expression induces apoptosis and inhibits cell migration in gastric cancer cells. Am J Physiol Gastrointest Liver Physiol. 2009;297:G385-96 pubmed publisher..p53 induces cell apoptosis and inhibits cell migration in part by downregulating TFF2 expression through an AP-1-like site, suggesting that TFF2 may be an important downstream target of p53. ..
- Lim J, Lee Y, Chun Y, Chen J, Kim J, Park J. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha. Mol Cell. 2010;38:864-78 pubmed publisher..Our results suggest that crosstalk between oxygen- and redox-responsive signal transducers occurs through the SIRT1-HIF-1alpha interaction. ..
- ..In this issue of Molecular Cell, Atanassov et al. (2009) show that the GCN5-containing SAGA complex regulates telomere function via deubiquitination and stabilization of the telomere repeat binding factor TRF1. ..
- Lackey D, Hoag K. Vitamin A upregulates matrix metalloproteinase-9 activity by murine myeloid dendritic cells through a nonclassical transcriptional mechanism. J Nutr. 2010;140:1502-8 pubmed publisher..Mmp-9 expression was enhanced through a transcriptional mechanism involving greater RARalpha promoter binding, recruitment of p300, and subsequent histone H3 acetylation, despite the absence of a consensus RARE. ..
- Zhu C, Qin Y, Xie D, Chua D, Fung J, Chen L, et al. Characterization of tumor suppressive function of P300/CBP-associated factor at frequently deleted region 3p24 in esophageal squamous cell carcinoma. Oncogene. 2009;28:2821-8 pubmed publisher..In conclusion, PCAF might be the target TSG responsible for the 3p24 deletion event, which has an important role in the development and progression of ESCC. ..
- Mooney S, Goel A, D Assoro A, Salisbury J, Janknecht R. Pleiotropic effects of p300-mediated acetylation on p68 and p72 RNA helicase. J Biol Chem. 2010;285:30443-52 pubmed publisher..In conclusion, our report has identified for the first time that acetylation modulates RNA helicases and provides multiple mechanisms how acetylation of p68 and p72 may affect normal and tumor cells. ..
- Kim J, Kim K, Youn B, Jin H, Kim N. MHC class II transactivator negatively regulates RANKL-mediated osteoclast differentiation by downregulating NFATc1 and OSCAR. Cell Signal. 2010;22:1341-9 pubmed publisher..Taken together, our data reveal that CIITA can act as a modulator of RANKL-induced osteoclastogenesis. ..
- Masatsugu T, Yamamoto K. Multiple lysine methylation of PCAF by Set9 methyltransferase. Biochem Biophys Res Commun. 2009;381:22-6 pubmed publisher..Our data may lead to a new insight into PCAF functions and provide additional information to identify unknown targets of Set9. ..
- Urvalek A, Wang X, Lu H, Zhao J. KLF8 recruits the p300 and PCAF co-activators to its amino terminal activation domain to activate transcription. Cell Cycle. 2010;9:601-11 pubmed..Taken together, these results identified the KLF8 activation domain located between residues 101-260 where the well-conserved Q118 and Q248 are essential for recruiting p300 and PCAF to activate target gene transcription. ..
- Llanos S, Cuadrado A, Serrano M. MSK2 inhibits p53 activity in the absence of stress. Sci Signal. 2009;2:ra57 pubmed publisher..Together, these findings constitute a new mechanism for the regulation of p53 transcriptional activity in response to stress. ..
- Nagy Z, Riss A, Fujiyama S, Krebs A, Orpinell M, Jansen P, et al. The metazoan ATAC and SAGA coactivator HAT complexes regulate different sets of inducible target genes. Cell Mol Life Sci. 2010;67:611-28 pubmed publisher..Interestingly, ATAC strongly influences the global phosphorylation level of histone H3S10, suggesting that in mammalian cells a cross-talk exists linking ATAC function to H3S10 phosphorylation. ..
- Genin P, Lin R, Hiscott J, Civas A. Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7. Mol Cell Biol. 2009;29:3435-50 pubmed publisher..This regulatory mechanism contributes to differential expression of IFN-A genes and may be critical for alpha interferon production in different cell types by RIG-I-dependent signals, leading to innate antiviral immune responses. ..
- Ferreon J, Martinez Yamout M, Dyson H, Wright P. Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein. Proc Natl Acad Sci U S A. 2009;106:13260-5 pubmed publisher..These observations reveal the molecular basis by which E1A inhibits p53-mediated transcriptional activation and provide a rationale for the efficiency of cellular transformation by the adenoviral E1A oncoprotein. ..
- Kashima H, Horiuchi A, Uchikawa J, Miyamoto T, Suzuki A, Ashida T, et al. Up-regulation of nuclear receptor corepressor (NCoR) in progestin-induced growth suppression of endometrial hyperplasia and carcinoma. Anticancer Res. 2009;29:1023-9 pubmed..Although progestins have been used for the treatment of endometrial neoplasias, the mechanisms of progestin-induced growth suppression remain undetermined...
- Kuninger D, Lundblad J, Semirale A, Rotwein P. A non-isotopic in vitro assay for histone acetylation. J Biotechnol. 2007;131:253-60 pubmed..This assay may be adapted readily for other substrates by simply generating new fusion proteins and for other acetyl-transferases by modifying reaction conditions. ..
- Polakowski N, Gregory H, Mesnard J, Lemasson I. Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain. Retrovirology. 2010;7:61 pubmed publisher..Consequently, the ability of HBZ to regulate expression of Dkk1 and possibly other cellular genes may only be significant during late stages of ATL, when Tax expression is repressed. ..
- Han Y, Jeong H, Jin Y, Kim Y, Jeong H, Yeo C, et al. Acetylation of histone deacetylase 6 by p300 attenuates its deacetylase activity. Biochem Biophys Res Commun. 2009;383:88-92 pubmed publisher..Our results demonstrate that p300 can inactivate HDAC6 by acetylation, and that p300 may regulate the activity of Sp1 indirectly through HDAC6 in addition to its direct modification of Sp1. ..
- Orpinell M, Fournier M, Riss A, Nagy Z, Krebs A, Frontini M, et al. The ATAC acetyl transferase complex controls mitotic progression by targeting non-histone substrates. EMBO J. 2010;29:2381-94 pubmed publisher..Thus, we have uncovered an essential function for ATAC in regulating Cyclin A activity and consequent mitotic progression. ..
- Shiota M, Yokomizo A, Tada Y, Uchiumi T, Inokuchi J, Tatsugami K, et al. P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance. Cancer Sci. 2010;101:1797-806 pubmed publisher..The present data suggest that Twist1 and YB-1 as well as PCAF may be promising molecular therapeutic targets. ..
- Shin S, Kim J, Baker A, Lim Y, Lee Y. Transcription factor Egr-1 is essential for maximal matrix metalloproteinase-9 transcription by tumor necrosis factor alpha. Mol Cancer Res. 2010;8:507-19 pubmed publisher..This report establishes that Egr-1 is essential for MMP-9 transcription in response to TNFalpha within the tumor microenvironment. ..
- Wethkamp N, Klempnauer K. Daxx is a transcriptional repressor of CCAAT/enhancer-binding protein beta. J Biol Chem. 2009;284:28783-94 pubmed publisher..Overall, our data identify Daxx as a new negative regulator of C/EBPbeta and provide first clues for a link between abrogation of Daxx-C/EBPbeta complex formation and APL remission. ..
- Erb M, Meinen S, Barzaghi P, Sumanovski L, Courdier Fruh I, Ruegg M, et al. Omigapil ameliorates the pathology of muscle dystrophy caused by laminin-alpha2 deficiency. J Pharmacol Exp Ther. 2009;331:787-95 pubmed publisher..These data qualify omigapil, which is in late phase of clinical development for human use, as a drug candidate for the treatment of MDC1A. ..
- Sinitsyna N, Reznikova T, Qin Q, Song H, Phillips M, Rice R. Arsenite suppression of involucrin transcription through AP1 promoter sites in cultured human keratinocytes. Toxicol Appl Pharmacol. 2010;243:275-82 pubmed publisher..These findings help trace a mechanism by which transcriptional effects of arsenite become manifest and help rationalize the unique action of arsenite, compared to the other agents, to preserve proliferative ability. ..
- Bowers E, Yan G, Mukherjee C, Orry A, Wang L, Holbert M, et al. Virtual ligand screening of the p300/CBP histone acetyltransferase: identification of a selective small molecule inhibitor. Chem Biol. 2010;17:471-82 pubmed publisher..Inhibition of histone acetylation and cell growth by C646 in cells validate its utility as a pharmacologic probe and suggest that p300/CBP HAT is a worthy anticancer target. ..
- Ravindra K, Selvi B, Arif M, Reddy B, Thanuja G, Agrawal S, et al. Inhibition of lysine acetyltransferase KAT3B/p300 activity by a naturally occurring hydroxynaphthoquinone, plumbagin. J Biol Chem. 2009;284:24453-64 pubmed publisher..This study describes for the first time the chemical entity (hydroxyl group) required for the inhibition of acetyltransferase activity...
- Cook K, Hilton S, Mecinovic J, Motherwell W, Figg W, Schofield C. Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1alpha (HIF-1alpha) and p300 by a zinc ejection mechanism. J Biol Chem. 2009;284:26831-8 pubmed publisher..The results have implications for the design of selective ETPs and for the interaction of ETPs with other zinc ion-binding protein targets involved in gene expression. ..
- Zeng L, Liu Y, Sha H, Chen H, Qi L, Smith J. XBP-1 couples endoplasmic reticulum stress to augmented IFN-beta induction via a cis-acting enhancer in macrophages. J Immunol. 2010;185:2324-30 pubmed publisher..Our findings have broader mechanistic implications for the pathogenesis of diseases involving ER stress and type I IFN, including viral infection, ischemia-reperfusion injury, protein misfolding, and inflammatory diseases. ..