title: 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.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Seok Young
authors.initials: SY
authors.lastname: Jang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000107:Acetylation / Q000187:drug effects; D047390:Casein Kinase II / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D045325:HCT116 Cells; D057809:HEK293 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D055550:Protein Stability / Q000187:drug effects; D021122:Protein Subunits / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D056572:Histone Deacetylase Inhibitors; D021122:Protein Subunits; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D047390:Casein Kinase II; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D008239:Lysine