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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Amino Acid Substitution, Animals, Apoptosis, Caspase 9, Caspases, Cell Line, Cells, Cultured, DNA Damage, Enzyme Activation, Gene Expression Profiling, Gene Expression Regulation, Humans, Mice, Mitochondria, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, RNA, Messenger, T-Lymphocytes, Tumor Suppressor Protein p53, bcl-2-Associated X Protein
Amino Acid Motifs, Amino Acid Sequence, Amino Acid Substitution, Animals, Apoptosis, Caspase 9, Caspases, Cell Line, Cells, Cultured, DNA Damage, Enzyme Activation, Gene Expression Profiling, Gene Expression Regulation, Humans, Mice, Mitochondria, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, RNA, Messenger, T-Lymphocytes, Tumor Suppressor Protein p53, bcl-2-Associated X Protein
Science
Date: May. 12, 2000
PubMed ID: 10807576
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