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Molecular and Cellular Biology, August 2001, p. 4929-4937, Vol. 21, No. 15
Department of Molecular Biology, Cell
Biology, and Biochemistry, Brown University, Providence, Rhode Island
02912
Received 13 February 2001/Returned for modification 10 April
2001/Accepted 28 April 2001
The c-myc proto-oncogene encodes a transcription factor
that participates in the regulation of cellular proliferation,
differentiation, and apoptosis. Ectopic overexpression of c-Myc has
been shown to sensitize cells to apoptosis. We report here that cells
lacking c-Myc activity due to disruption of the c-myc gene
by targeted homologous recombination are defective in DNA
damage-initiated apoptosis in the G2 phase of the cell
cycle. The downstream effector of c-Myc is cyclin A, whose ectopic
expression in c-myc
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.15.4929-4937.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
c-Myc Is Necessary for DNA Damage-Induced
Apoptosis in the G2 Phase of the Cell Cycle


/
cells rescues the
apoptosis defect. The kinetics of the G2 response indicate
that the induction of cyclin A and the concomitant activation of Cdk2
represent an early step during commitment to apoptosis. In contrast,
expression of cyclins E and D1 does not rescue the apoptosis defect,
and apoptotic processes in G1 phase are not affected in
c-myc
/
cells. These observations link DNA
damage-induced apoptosis with cell cycle progression and implicate
c-Myc in the functioning of a subset of these pathways.
*
Corresponding author. Mailing address: Department of
Molecular Biology, Cell Biology, and Biochemistry, Box G-J223, Brown University, Providence, RI 02912. Phone: (401) 863-9654. Fax: (401)
863-9653. E-mail: john_sedivy{at}brown.edu.
Present address: Second Department of Medicine, Tokyo Medical and
Dental University, Tokyo 113, Japan.
Present address: Area de Fisiologia, Facultad de Medicina,
Universidad de Oviedo, Oviedo 33006, Spain.
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