Probing p300/CBP Associated Factor (PCAF)-Dependent Pathways with a Small Molecule Inhibitor
详细信息 查看全文
- 作者：Rahul Modak ; Jeelan Basha ; Narendra Bharathy ; Koustav Maity ; Pushpak Mizar ; Akshay V. Bhat ; Madavan Vasudevan ; Vinay Kumar Rao ; Wai Kay Kok ; Nagashayana Natesh ; Reshma Taneja ; Tapas K. Kundu
- 刊名：ACS Chemical Biology
- 出版年：2013
- 出版时间：June 21, 2013
- 年：2013
- 卷：8
- 期：6
- 页码：1311-1323
- 全文大小：937K
- 年卷期：v.8,no.6(June 21, 2013)
- ISSN：1554-8937
文摘
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.