Human Immunodeficiency Virus Type 1 Nef Binds to Tumor Suppressor p53 and Protects Cells against p53-Mediated Apoptosis
| Autor: | Sonia E. Sankovich, John Mills, Dale A. McPhee, Alison L. Greenway, Ricky W. Johnstone, Paul F. Lambert, Kelly Allen, Gavan Holloway, Ahmed A. Azad |
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| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
Transcriptional Activation Multiprotein complex Ultraviolet Rays viruses Immunology Apoptosis Biology Microbiology Gene Products nef law.invention Gene product law Virology Tumor Cells Cultured Humans nef Gene Products Human Immunodeficiency Virus Gene Kinase virus diseases In vitro Virus-Cell Interactions Cell biology Insect Science HIV-1 Suppressor Tumor Suppressor Protein p53 Function (biology) |
| Zdroj: | Journal of Virology. 76:2692-2702 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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