PUMA, a Novel Proapoptotic Gene, Is Induced by p53

Mol Cell. 2001 Mar;7(3):683-94. doi: 10.1016/s1097-2765(01)00214-3.

Abstract

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.

MeSH terms

  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Apoptosis*
  • Base Sequence
  • Binding Sites
  • Caspase 3
  • Caspase 9
  • Caspases / metabolism
  • Cell Cycle Proteins*
  • Cell Division
  • Cell Line
  • Cloning, Molecular
  • Cytochrome c Group / metabolism
  • DNA / genetics
  • DNA / metabolism
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • Exons / genetics
  • Helminth Proteins*
  • Humans
  • Introns / genetics
  • Mitochondria / chemistry
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cell Cycle Proteins
  • Cytochrome c Group
  • Enzyme Precursors
  • Helminth Proteins
  • Nuclear Proteins
  • PUMA1 protein, Parascaris univalens
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • DNA
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases

Associated data

  • GENBANK/AF354654
  • GENBANK/AF354655
  • GENBANK/AF354656