PUMA, a novel proapoptotic gene, is induced by p53.
The p53 tumor-suppressor protein functions as a transcriptional activator, and several p53-inducible genes that play a role in the induction of apoptosis in response to p53 have been described. We have identified a novel gene named PUMA (p53 upregulated modulator of apoptosis) as a target for activation by p53. This gene encodes two BH3 domain-containing proteins (PUMA-alpha and PUMA-beta) that are induced in cells following p53 activation. PUMA-alpha and PUMA-beta show similar activities; they bind to Bcl-2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death. Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway.
Nakano
K
K
Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Maryland 21702, USA.
Vousden
K H
KH
D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D017209:Apoptosis; D001483:Base Sequence; D001665:Binding Sites; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D002460:Cell Line; D003001:Cloning, Molecular; D003574:Cytochrome c Group / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005091:Exons / Q000235:genetics; D015801:Helminth Proteins; D006801:Humans; D007438:Introns / Q000235:genetics; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018797:Cell Cycle Proteins; D003574:Cytochrome c Group; D004792:Enzyme Precursors; D015801:Helminth Proteins; D009687:Nuclear Proteins; C112738:PUMA1 protein, Parascaris univalens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004247:DNA; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases