p53 - A pro-apoptotic signal transducer involved in AIDS

Maria Castedo, Jean Luc Perfettini, Mauro Piacentini, Guido Kroemer

Research output: Contribution to journalArticle

Abstract

P53 is a well-characterized tumor suppressor protein, which can induce apoptosis, either by inducing transcription of pro-apoptotic genes or by direct effects on mitochondrial membranes. Roughly 50% of human cancers are affected by the genetic or epigenetic inactivation of p53. Recently, p53 has been incriminated to play a cardinal role in the destruction of the immune system by human immunodeficiency virus (HIV-1) infection. This suspicion is based on several lines of evidence: (i) p53 exhibits activating phosphorylations in a subset of peripheral blood mononuclear cells and lymph node cells from HIV-1 carriers; (ii) some p53 target genes (e.g., PUMA, a pro-apoptotic member of the Bcl-2 family) are overexpressed in HIV-1 carriers; (iii) in vitro, p53 and/or PUMA are rate-limiting for the induction of cell death by HIV-1 infection or, in particular, by the HIV-1 Envelope (Env), in a variety of model systems, including the apoptosis of syncytia elicited by Env or cell death induced by the Env constituent gp120. Thus, p53 may constitute a novel therapeutic target for the treatment of AIDS.

Original languageEnglish
Pages (from-to)701-706
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume331
Issue number3
DOIs
Publication statusPublished - Jun 10 2005

Keywords

  • Bax
  • HIV-1
  • Mitochondria
  • NF-κB
  • Puma

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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