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DC Field | Value | Language |
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dc.contributor.author | Banerjea, Akhil C | - |
dc.contributor.author | Raja, Rameez | - |
dc.contributor.author | Ronsard, Larance | - |
dc.contributor.author | Lata, Sneh | - |
dc.contributor.author | Trivedi, Shubhendu | - |
dc.date.accessioned | 2022-08-18T10:08:00Z | - |
dc.date.available | 2022-08-18T10:08:00Z | - |
dc.date.issued | 2017-07 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/1402 | - |
dc.description.abstract | Murine double minute 2 (Mdm2) is known to enhance the transactivation potential of human immunodeficiency virus (HIV-1) Tat protein by causing its ubiquitination. However, the regulation of Mdm2 during HIV-1 infection and its implications for viral replication have not been well studied. Here, we show that the Mdm2 protein level increases during HIV-1 infection and this effect is mediated by HIV-1 Tat protein. Tat appears to stabilise Mdm2 at the post-translational level by inducing its phosphorylation at serine-166 position through AKT. Although p53 is one of the key players for Mdm2 induction, Tat-mediated stabilisation of Mdm2 appears to be independent of p53. Moreover, the non-phosphorylatable mutant of Mdm2 (S166A) fails to interact with Tat and shows decreased half-life in the presence of Tat compared with wild-type Mdm2. Furthermore, the non-phosphorylatable mutant of Mdm2 (S166A) is unable to support HIV-1 replication. Thus, HIV-1 Tat appears to stabilise Mdm2, which in turn enhances Tat-mediated viral replication. This study highlights the importance of post-translational modifications of host cellular factors in HIV-1 replication and pathogenesis. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Portland Press Limited | en_US |
dc.subject | HIV-1 replication; Mdm2; Tat; phosphorylation | en_US |
dc.title | HIV-1 Tat potently stabilises Mdm2 and enhances viral replication | en_US |
dc.type | Article | en_US |
dc.journal | Biochem J | en_US |
dc.volumeno | 474 | en_US |
dc.issueno | 14 | en_US |
dc.pages | 2449-2464 | en_US |
Appears in Collections: | Virology- II, Publications |
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File | Description | Size | Format | |
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bcj-2016-0825.pdf | 1.19 MB | Adobe PDF | View/Open Request a copy |
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