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

Yoichi Ohiro, Igor Garkavtsev, Shinichiro Kobayashi, Kodangattil R. Sreekumar, Regan Nantz, Bryan T. Higashikubo, Shannon L. Duffy, Ryuji Higashikubo, Anny Usheva, David Gius, Nikolai Kley, Nobuo Horikoshi

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)163-171
Number of pages9
JournalFEBS Letters
Volume524
Issue number1-3
DOIs
StatePublished - Jul 31 2002

Keywords

  • Apoptosis
  • Cloning
  • Oxidoreductase
  • Target gene
  • Transcription
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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