A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)

FEBS Lett. 2002 Jul 31;524(1-3):163-71. doi: 10.1016/s0014-5793(02)03049-1.

Abstract

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Apoptosis Inducing Factor
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Binding Sites
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10
  • Cloning, Molecular
  • DNA
  • Flavoproteins / genetics*
  • Gene Expression Regulation / physiology*
  • Genes, Reporter
  • Humans
  • In Situ Hybridization, Fluorescence
  • Membrane Proteins / genetics*
  • Mitochondrial Proteins*
  • Molecular Sequence Data
  • Proteins / chemistry
  • Proteins / genetics*
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • AIFM1 protein, human
  • AIFM2 protein, human
  • Apoptosis Inducing Factor
  • Apoptosis Regulatory Proteins
  • Flavoproteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Adenosine Diphosphate
  • DNA