Research Project
Grant-in-Aid for Research Activity Start-up
A zinc finger protein GATA4 is associates with an intrinsic histone acetyltransferase p300 and regulates myocardial transcriptional activities in response to hypertrophic stimuli. We found that Retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48/46) are novel component of the p300/GATA4 complex and form a repressor complex with HDACs in cardiomyocytes. RbAp48/46 could bind to GATA4, mediate the binding of HDAC1/2 with GATA4, and inhibited phenylephrine-induced hypertrophic responses such as acetylation of GATA4, activation of the ANF and ET-1 promoters, and increase in cell size. On the contrary, knockdown of RbAp48/46 by shRNA augmented such responses. Knockdown of HDAC1/2 augmented PE-induced hypertrophy and failed to inhibitory effects by RbAp48/46.These findings demonstrate that RbAp48/46 recruit HDAC1/2 onto GATA4, suppress the binding of p300 with GATA4, and inhibit hypertrophic responses in cardiomyocytes.
All 2014 2013 2012 Other
All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (20 results) Book (4 results) Remarks (1 results)
Biol Pharm Bull
Volume: 96 Pages: 1708-1714
Biological and Pharmaceutical Bulletin
Volume: 36 Issue: 1 Pages: 13-17
10.1248/bpb.b212022
130003361361
