The Cell Cycle Factor E2F-1 Activates Bnip3 and the Intrinsic Death Pathway in Ventricular Myocytes

The cell cycle factor E2F-1 is known to regulate a variety of cellular processes including apoptosis. Previously we showed that disruption of Rb–E2F-1 complexes provoked apoptosis of postmitotic adult and neonatal ventricular myocytes; however, the underlying mechanism was undetermined. In this repo...

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Bibliographic Details
Published in:Circulation research 2008-02, Vol.102 (4), p.472-479
Main Authors: Yurkova, Natalia, Shaw, James, Blackie, Karen, Weidman, Danielle, Jayas, Ravi, Flynn, Bryan, Kirshenbaum, Lorrie A
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Biological and medical sciences
Cell Cycle - physiology
Cells, Cultured
E2F1 Transcription Factor - genetics
E2F1 Transcription Factor - metabolism
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - physiology
Hypoxia - metabolism
Hypoxia - physiopathology
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mitochondria - physiology
Mitochondrial Proteins
Myocytes, Cardiac - cytology
Myocytes, Cardiac - physiology
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction - physiology
Transcriptional Activation - physiology
Transfection
Vertebrates: cardiovascular system
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Summary:The cell cycle factor E2F-1 is known to regulate a variety of cellular processes including apoptosis. Previously we showed that disruption of Rb–E2F-1 complexes provoked apoptosis of postmitotic adult and neonatal ventricular myocytes; however, the underlying mechanism was undetermined. In this report, we show that E2F-1 provokes cell death of ventricular myocytes through a mechanism that directly impinges on the intrinsic death pathway. Furthermore, we show mechanistically that the hypoxia-inducible death factor Bnip3 is a direct transcriptional target of E2F-1 that is necessary and sufficient for E2F-1–induced cell death. Expression of E2F-1 resulted in a 4.9-fold increase (P
ISSN:0009-7330
1524-4571
DOI:10.1161/CIRCRESAHA.107.164731