Hashimoto Akiko, Hirose Kenzo, Iino Masamitsu
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Biol Chem. 2005 Jul 15;280(28):26225-32. doi: 10.1074/jbc.M409363200. Epub 2005 May 18.
BAD, a member of the Bcl-2 protein family, promotes mitochondria-dependent apoptosis. Here, we report that BAD dissociates from 14-3-3zeta at each G2/M phase of proliferating lymphoid cells. The cell cycle-dependent dissociation of BAD was associated with phosphorylation at Ser-128, whereas mutant S128A-BAD, in which Ser-128 was converted to alanine, remained associated with 14-3-3zeta throughout the cell cycle. Although the cell cycle-dependent dissociation of BAD per se did not induce apoptosis, growth factor deprivation induced prompt apoptosis at the G2/M phase but not at the G1 phase. In cells expressing S128A-BAD, growth factor deprivation-induced apoptosis was markedly delayed and was accompanied by a delayed dephosphorylation of growth factor-dependent regulatory serine residues. These results indicate that BAD induces apoptosis upon detecting the coincidence of G2/M phase and growth factor deprivation.
