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| == Function == | | == Function == |
| [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref> | | [https://www.uniprot.org/uniprot/CBP_HUMAN CBP_HUMAN] Acetylates histones, giving a specific tag for transcriptional activation. Also acetylates non-histone proteins, like NCOA3 and FOXO1. Binds specifically to phosphorylated CREB and enhances its transcriptional activity toward cAMP-responsive genes. Acts as a coactivator of ALX1 in the presence of EP300.<ref>PMID:9707565</ref> <ref>PMID:11154691</ref> <ref>PMID:12738767</ref> <ref>PMID:12929931</ref> |
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| == Publication Abstract from PubMed ==
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| Covalent modification of histones is a fundamental mechanism of regulated gene expression in eukaryotes, and interpretation of histone modifications is an essential feature of epigenetic control. Bromodomains are specialized binding modules that interact with acetylated histones, linking chromatin recognition to gene transcription. Due to their ability to function in a domain-specific fashion, selective disruption of bromodomain:acetylated histone interactions with chemical probes serves as a powerful means for understanding biological processes regulated by these chromatin adaptors. Here we describe the discovery and characterization of potent and selective small molecule inhibitors for the bromodomains of CREBBP/EP300 that engage their target in cellular assays. We use these tools to demonstrate a critical role for CREBBP/EP300 bromodomains in regulatory T cell biology. Since regulatory T cell recruitment to tumors is a major mechanism of immune evasion by cancer cells, our data highlight the importance of CREBBP/EP300 bromodomain inhibition as a novel, small molecule-based approach for cancer immunotherapy.
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| Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.,Ghosh S, Taylor A, Chin M, Huang HR, Conery AR, Mertz JA, Salmeron A, Dakle PJ, Mele D, Cote A, Jayaram H, Setser JW, Poy F, Hatzivassiliou G, DeAlmeida-Nagata D, Sandy P, Hatton C, Romero FA, Chiang E, Reimer T, Crawford T, Pardo E, Watson VG, Tsui V, Cochran AG, Zawadzke L, Harmange JC, Audia JE, Bryant BM, Cummings RT, Magnuson SR, Grogan JL, Bellon SF, Albrecht BK, Sims RJ 3rd, Lora JM J Biol Chem. 2016 Apr 7. pii: jbc.M115.708560. PMID:27056325<ref>PMID:27056325</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| ==See Also== | | ==See Also== |