Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Motifs
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Apoptosis*
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Caspase 9
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Caspases / metabolism
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Cell Line
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Cells, Cultured
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DNA Damage
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Enzyme Activation
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Gene Expression Profiling
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Gene Expression Regulation
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Humans
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Mice
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Mitochondria / metabolism
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Molecular Sequence Data
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / chemistry
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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T-Lymphocytes / metabolism
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Tumor Suppressor Protein p53 / physiology*
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bcl-2-Associated X Protein
Substances
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PMAIP1 protein, human
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Pmaip1 protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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CASP9 protein, human
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Casp9 protein, mouse
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Caspase 9
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Caspases
Associated data
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GENBANK/AB041230
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GENBANK/AB041231