Identification of a caspase 3-independent role of pro-apoptotic factor Bak in TNF-alpha-induced apoptosis.
By using our recently developed gene discovery system, we have identified Bak, a member of the Bcl-2 family, as a pro-apoptotic factor in the tumor necrosis factor (TNF)-alpha-induced apoptotic pathway in caspase 3-deficient cells. Unlike Bcl-2, Bak stimulates several apoptotic pathways, however the molecular mechanism(s) of its action remains unclear. For example, it is unclear whether Bak induces apoptosis in caspase 3-deficient cells. In this study, we examined the effects of overexpression of Bak in MCF-7 cells that lack caspase 3. We found that despite the absence of caspase 3 in MCF-7 cells, they were more sensitive to the cell death effects of Bak as compared to caspase 3-expressing HeLa S3 cells. The targeting of Bak function by ribozymes suggests that Bak is required for the TNF-alpha-induced apoptotic pathway in caspase 3-deficient cells. This study demonstrates the caspase 3-independent function of Bak in the TNF-alpha-induced apoptotic pathway.
Suyama
Eigo
E
Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Hongo, Japan.
Kawasaki
Hiroaki
H
Taira
Kazunari
K
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D001483:Base Sequence; D053148:Caspase 3; D020169:Caspases / Q000172:deficiency / Q000502:physiology*; D002460:Cell Line; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D050998:bcl-2 Homologous Antagonist-Killer Protein
C494772:BAK1 protein, human; D008164:Luminescent Proteins; D008565:Membrane Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D050998:bcl-2 Homologous Antagonist-Killer Protein; D049452:Green Fluorescent Proteins; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases