Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis.
A critical function of tumor suppressor p53 is the induction of apoptosis in cells exposed to noxious stresses. We report a previously unidentified pro-apoptotic gene, Noxa. Expression of Noxa induction in primary mouse cells exposed to x-ray irradiation was dependent on p53. Noxa encodes a Bcl-2 homology 3 (BH3)-only member of the Bcl-2 family of proteins; this member contains the BH3 region but not other BH domains. When ectopically expressed, Noxa underwent BH3 motif-dependent localization to mitochondria and interacted with anti-apoptotic Bcl-2 family members, resulting in the activation of caspase-9. We also demonstrate that blocking the endogenous Noxa induction results in the suppression of apoptosis. Noxa may thus represent a mediator of p53-dependent apoptosis.
Oda
E
E
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Ohki
R
R
Murasawa
H
H
Nemoto
J
J
Shibue
T
T
Yamashita
T
T
Tokino
T
T
Taniguchi
T
T
Tanaka
N
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004249:DNA Damage; D004789:Enzyme Activation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D051028:bcl-2-Associated X Protein
C498702:PMAIP1 protein, human; C408009:Pmaip1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases