title: Bnip3 Binds and Activates p300: Possible Role in Cardiac Transcription and Myocyte Morphology.
abstract: Bnip3 is a hypoxia-regulated member of the Bcl-2 family of proteins that is implicated in apoptosis, programmed necrosis, autophagy and mitophagy. Mitochondria are thought to be the primary targets of Bnip3 although its activities may extend to the ER, cytoplasm, and nucleus. Bnip3 is induced in the heart by ischemia and pressure-overload, and may contribute to cardiomyopathy and heart failure. Only mitochondrial-dependent programmed death actions have been described for Bnip3 in the heart. Here we describe a novel activity of Bnip3 in cultured cardiac myocytes and transgenic mice overexpressing Bnip3 in the heart (Bnip3-TG). In cultured myocytes Bnip3 bound and activated the acetyltransferase p300, increased acetylation of histones and the transcription factor GATA4, and conferred p300 and GATA4-sensitive cellular morphological changes. In intact Bnip3-TG hearts Bnip3 also bound p300 and GATA4 and conferred enhanced GATA4 acetylation. Bnip3-TG mice underwent age-dependent ventricular dilation and heart failure that was partially prevented by p300 inhibition with curcumin. The results suggest that Bnip3 regulates cardiac gene expression and perhaps myocyte morphology by activating nuclear p300 acetyltransferase activity and hyperacetylating histones and p300-selective transcription factors.
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: John W
authors: JW
authors: Thompson
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Jianqin
authors: J
authors: Wei
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Kweku
authors: K
authors: Appau
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Huilan
authors: H
authors: Wang
authors: Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Hong
authors: H
authors: Yu
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Maria G
authors: MG
authors: Spiga
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Regina M
authors: RM
authors: Graham
authors: Department of Molecular and Cellular Pharmacology and the Vascular Biology Institute, University of Miami Miller School of Medicine, Miami, Florida, United States of America.
authors: Keith A
authors: KA
authors: Webster
mesh_terms: D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D050991:GATA4 Transcription Factor / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050991:GATA4 Transcription Factor; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C505650:BNIP3 protein, rat; C508686:BNip3 protein, mouse; C484171:Gata4 protein, mouse; C084365:Gata4 protein, rat