P53 deacetylation by SIRT1 decreases during protein kinase CKII downregulation-mediated cellular senescence

Abstract

Cellular senescence is thought to be an important tumor suppression process in vivo. We have previously shown that p53 activation is necessary for CKII inhibition-mediated cellular senescence. Here, CKII inhibition induced acetylation of p53 at K382 in HCT116 and HEK293 cells. This acetylation event was suppressed by SIRT1 activation. CKIIα and CKIIβ were co-immunoprecipitated with SIRT1 in a p53-independent manner. Maltose binding protein pull-down and yeast two-hybrid indicated that SIRT1 bound to CKIIβ, but not to CKIIα. CKII inhibition reduced SIRT1 activity in cells. CKII phosphorylated and activated human SIRT1 in vitro. Finally, SIRT1 overexpression antagonized CKII inhibition-mediated cellular senescence. These results reveal that CKII downregulation induces p53 stabilization by negatively regulating SIRT1 deacetylase activity during senescence. Structured summary of protein interactionsCKII Betabinds to SIRT1 by pull down (View interaction)CKII Betaphysically interacts with SIRT1 by pull down (View interaction)SIRT1physically interacts with CKII Beta and CKII Alpha by anti bait coimmunoprecipitation (View Interaction: 1, 2, 3)CKII Betaphysically interacts with SIRT1 by two hybrid (View interaction)