Probing p300/CBP associated factor (PCAF)-dependent pathways with a small molecule inhibitor.
ACS Chem Biol, 2013;8(6):1311-23.
Modak R[1], Basha J, Bharathy N, Maity K, Mizar P, Bhat AV, Vasudevan M, Rao VK, Kok WK, Natesh N, Taneja R, Kundu TK
Affiliations
PMID: 23570531DOI: 10.1021/cb4000597
Impact factor: 4.634
Abstract
PCAF (KAT2B) belongs to the GNAT family of lysine acetyltransferases (KAT) and specifically acetylates the histone H3K9 residue and several nonhistone proteins. PCAF is also a transcriptional coactivator. Due to the lack of a PCAF KAT-specific small molecule inhibitor, the exclusive role of the acetyltransferase activity of PCAF is not well understood. Here, we report that a natural compound of the hydroxybenzoquinone class, embelin, specifically inhibits H3Lys9 acetylation in mice and inhibits recombinant PCAF-mediated acetylation with near complete specificity in vitro. Furthermore, using embelin, we have identified the gene networks that are regulated by PCAF during muscle differentiation, further highlighting the broader regulatory functions of PCAF in muscle differentiation in addition to the regulation via MyoD acetylation.
MeSH terms
Acetylation; Animals; Benzoquinones; Cell Differentiation; Cell Line; Gene Expression Regulation; HEK293 Cells; Histones; Humans; Mice; MyoD Protein; Myoblasts; Recombinant Proteins; p300-CBP Transcription Factors
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