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(Circulation Research. 2008;102:395.)
© 2008 American Heart Association, Inc.

Editorials

Discovery of an Intricate Balance

Gene Transcription, Cell Cycle, and Apoptosis

Jennifer L. Hall

From the Lillehei Heart Institute, University of Minnesota, Minneapolis.

Correspondence to Jennifer L. Hall, PhD, Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455. E-mail jlhall@umn.edu

See related article, pages 472–479

Key Words: E2F-1 • cell cycle • DNA synthesis • Bnip3 • hypoxia • retinoblastoma • Rb • myocyte

An extract of the first 250 words of the full text is provided, because this article has no abstract.

In this issue of Circulation Research, Yurkova et al¹ present direct 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 Schneider, 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 death signaling pathway under conditions of hypoxia (Figure).¹ Thus, 10 years ago, Kirshenbaum and colleagues published findings causing us to reexamine the predefined 1-dimensional role of E2F-1 as a cell cycle regulatory factor and consider E2F-1 as a multidimensional protein with the ability to regulate both cell cycle and intrinsic cell death pathways. In this issue of Circulation Research, Yurkova et al have discovered that E2F-1 binds the promoter region of a cell death gene and promotes apoptosis.

View larger version (47K):   Figure. Schematic depicting the new findings reported by Yurkova et al in this issue of Circulation Research.1 Under normoxic conditions in the . . . [Full Text of this Article]

Related Article:

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

Natalia Yurkova, James Shaw, Karen Blackie, Danielle Weidman, Ravi Jayas, Bryan Flynn, and Lorrie A. Kirshenbaum
Circ. Res. 2008 102: 472-479. [Abstract] [Full Text] [PDF]