2013 Fiscal Year Final Research Report
Analysis of novel p300/GATA4 binding complex druing cardiomyocyte hypertrophy by proteomics approach
| Project/Area Number |
24890191
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | 心肥大 / 転写因子 / GATA4 / p300 / 翻訳後修飾 |
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| Research Abstract |
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.
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