Advertisement

 

 

HIV-1 Tat potently stabilises Mdm2 and enhances viral replication.

HIV-1 Tat potently stabilises Mdm2 and enhances viral replication.
Author Information (click to view)

Raja R, Ronsard L, Lata S, Trivedi S, Banerjea AC,


Raja R, Ronsard L, Lata S, Trivedi S, Banerjea AC, (click to view)

Raja R, Ronsard L, Lata S, Trivedi S, Banerjea AC,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

The Biochemical journal 2017 07 11474(14) 2449-2464 doi 10.1042/BCJ20160825

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

nine + eleven =

[ HIDE/SHOW ]