Discovery of an Intricate Balance: Gene Transcription, Cell Cycle, and Apoptosis. Circ Res

In this issue of Circulation Research, Yurkova et al1 presentdirect evidence that a cell cycle regulatory factor, E2F-1, binds to a proapoptotic gene in hypoxic cardiac myocytes, leading to apoptosis. Life embraces death. The role of the cell cycle regulatory protein E2F-1 in a postmitotic cardiac myocyte has remained somewhat of a mystery. In 1997, while working in the laboratory of Schnei-der, Kirshenbaum and colleagues uncovered a critical clue. Cardiac myocytes overexpressing E2F-1 entered the cell cycle and headed for the grave.2,3 This work was among the first to lead a wave of evidence across disciplines to support a role for E2F-1 in the cell cycle and cell death.4 However, the mechanism(s) by which E2F-1 promotes apoptosis have remained unclear. Kirshenbaum has returned. This time with the discovery that E2F-1 binds to the promoter region of Bnip3, an apoptotic gene, promoting an intrinsic cell deat