Abundance of cyclin B1 regulates gamma-radiation-induced apoptosis.
gamma-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating gamma-radiation-induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage. Cyclin B1 is the regulatory subunit of the cdc2 serine/threonine kinase, and accumulation of cyclin B1 in late G2 phase of the cell cycle is a prerequisite for mitotic initiation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP16, HL60, thymocytes) undergoing gamma-radiation-induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibition of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expression is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for gamma-radiation-induced apoptosis. (Blood. 2000;95:2645-2650)
Porter
L A
LA
Hamilton Regional Cancer Center, Hamilton, Ontario, Canada.
Singh
G
G
Lee
J M
JM
D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D016203:CDC2 Protein Kinase / Q000502:physiology; D019926:Cyclin B / Q000502:physiology*; D056744:Cyclin B1; D005720:Gamma Rays; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D015398:Signal Transduction / Q000528:radiation effects
C534699:CCNB1 protein, human; C534700:Ccnb1 protein, mouse; D019926:Cyclin B; D056744:Cyclin B1; D016203:CDC2 Protein Kinase