title: BAD detects coincidence of G2/M phase and growth factor deprivation to regulate apoptosis.
abstract: 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.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hashimoto
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hirose
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iino
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry; D000409:Alanine / Q000737:chemistry; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005434:Flow Cytometry; D031541:Fluorescence Resonance Energy Transfer; D016193:G1 Phase; D016195:G2 Phase; D015723:Gene Library; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007377:Interleukin-3 / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance; D013997:Time Factors; D051025:bcl-Associated Death Protein
chemical_list: D048948:14-3-3 Proteins; C494819:BAD protein, human; D001426:Bacterial Proteins; C494820:Bad protein, mouse; D002352:Carrier Proteins; C485182:Cyan Fluorescent Protein; D018076:DNA, Complementary; D006133:Growth Substances; D007377:Interleukin-3; D008164:Luminescent Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051025:bcl-Associated Death Protein; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; D012694:Serine; D000409:Alanine; D015739:Nocodazole