%0 Journal Article
%T Phosphatase PPM1A negatively regulates P-TEFb function in resting CD4+ T cells and inhibits HIV-1 gene expression
%A Sona Budhiraja
%A Rajesh Ramakrishnan
%A Andrew P Rice
%J Retrovirology
%D 2012
%I BioMed Central
%R 10.1186/1742-4690-9-52
%X We found that overexpression of PPM1A inhibits HIV-1 gene expression during viral infection and this required PPM1A catalytic function. Using an artificial CDK tethering system, we further found that PPM1A inhibits CDK9, but not CDK8 mediated activation of the HIV-1 LTR. SiRNA depletion of PPM1A in resting CD4+T cells increased the level of CDK9 T-loop phosphorylation and enhanced HIV-1 gene expression. We also observed that PPM1A protein levels are relatively high in resting CD4+T cells and are not up-regulated upon T cell activation.Our results establish a functional link between HIV-1 replication and modulation of CDK9 T-loop phosphorylation by PPM1A. PPM1A represses HIV-1 gene expression by inhibiting CDK9 T-loop phosphorylation, thus reducing the amount of active P-TEFb available for recruitment to the viral LTR. We also infer that PPM1A enzymatic activity in resting and activated CD4+ T cells are likely regulated by as yet undefined factors.
%K P-TEFb
%K HIV-1
%K CDK9
%K PPM1A
%U http://www.retrovirology.com/content/9/1/52/abstract