p53-A pro-apoptotic signal transducer involved in AIDS.
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.
Castedo
Maria
M
CNRS-UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France.
Perfettini
Jean-Luc
JL
Piacentini
Mauro
M
Kroemer
Guido
G
D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D016158:Genes, p53; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D015658:HIV Infections / Q000503:physiopathology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000502:physiology; D008928:Mitochondria / Q000502:physiology / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D015699:HIV Envelope Protein gp120; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53