Abstract
Through global profiling of genes that were expressed soon after p53 expression, we identified a novel gene termed PUMA (p53 upregulated modulator of apoptosis). The protein encoded by PUMA was found to be exclusively mitochondrial and to bind to Bcl-2 and Bcl-X(L) through a BH3 domain. Exogenous expression of PUMA resulted in an extremely rapid and profound apoptosis that occurred much earlier than that resulting from exogenous expression of p53. Based on its unique expression patterns, p53 dependence, and biochemical properties, PUMA may be a direct mediator of p53-associated apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis*
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Binding Sites
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Cell Cycle Proteins*
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Cell Division
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Cell Line
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Cloning, Molecular
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Colorectal Neoplasms / metabolism*
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Colorectal Neoplasms / pathology*
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Gene Expression Profiling
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Gene Expression Regulation
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Genes, Lethal / genetics
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Genes, Reporter
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Helminth Proteins*
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Humans
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Mice
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Mitochondria / chemistry
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Mitochondria / metabolism
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Promoter Regions, Genetic / genetics
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Bcl2l1 protein, mouse
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Cell Cycle Proteins
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Helminth Proteins
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Nuclear Proteins
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PUMA1 protein, Parascaris univalens
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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-X Protein
Associated data
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GENBANK/AF332558
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GENBANK/AF332559
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GENBANK/AF332560
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GENBANK/AF332561