title: Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis.
abstract: The nef gene product of human immunodeficiency virus type 1 (HIV-1) is important for the induction of AIDS, and key to its function is its ability to manipulate T-cell function by targeting cellular signal transduction proteins. We reported that Nef coprecipitates a multiprotein complex from cells which contains tumor suppressor protein p53. We now show that Nef interacts directly with p53. Binding assays showed that an N-terminal, 57-residue fragment of Nef (Nef 1-57) contains the p53-binding domain. Nef also interacted with p53 during HIV-1 infection in vitro. As p53 plays a critical role in the regulation of apoptosis, we hypothesized that Nef may alter this process. Nef inhibited UV light-induced, p53-dependent apoptosis in MOLT-4 cells, with Nef 1-57 being as effective as its full-length counterpart. The inhibition by Nef of p53 apoptotic function is most likely due its observed ability to decrease p53 protein half-life and, consequently, p53 DNA binding activity and transcriptional activation. These data show that HIV-1 Nef may augment HIV replication by prolonging the viability of infected cells by blocking p53-mediated apoptosis.
authors.affiliation: AIDS Cellular Biology Unit, Macfarlane Burnet Centre for Medical Research, Fairfield, Victoria 3078, Australia. greenway@burnet.edu.au
authors.forename: Alison L
authors.initials: AL
authors.lastname: Greenway
authors.forename: Dale A
authors.initials: DA
authors.lastname: McPhee
authors.forename: Kelly
authors.initials: K
authors.lastname: Allen
authors.forename: Ricky
authors.initials: R
authors.lastname: Johnstone
authors.forename: Gavan
authors.initials: G
authors.lastname: Holloway
authors.forename: John
authors.initials: J
authors.lastname: Mills
authors.forename: Ahmed
authors.initials: A
authors.lastname: Azad
authors.forename: Sonia
authors.initials: S
authors.lastname: Sankovich
authors.forename: Paul
authors.initials: P
authors.lastname: Lambert
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D016159:Tumor Suppressor Protein p53; D054311:nef Gene Products, Human Immunodeficiency Virus