Abundance of cyclin B1 regulates gamma-radiation-induced apoptosis

gamma-Radiation is a potent inducer of apoptosis. There are multiple pathwa ys regulating DNA damage-induced apoptosis, and we set out to identify nove l 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 regul atory subunit of the cdc2 serine/threonine kinase, and accumulation of cycl in B1 in late G2 phase of the cell cycle is a prerequisite for mitotic init iation in mammalian cells. We find that abundance of the cyclin B1 protein rapidly increases in several mouse and human hematopoietic cells (Ramos, DP 16, HL60, thymocytes) undergoing gamma-radiation-induced apoptosis. Cyclin B1 accumulation occurs in all phases of the cell cycle. Antisense inhibitio n of cyclin B1 accumulation decreases apoptosis, and ectopic cyclin B1 expr ession is sufficient to induce apoptosis. These observations are consistent with the idea that cyclin B1 is both necessary and sufficient for gamma-ra diation-induced apoptosis. (Blood. 2000;95:2645-2650) (C) 2000 by The Ameri can Society of Hematology.