title: Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation.
abstract: Sirtuins are evolutionarily conserved NAD(+)-dependent deacetylases and ADP-ribosyltransferases involved in the regulation of cell division, apoptosis, DNA damage repair, genomic silencing, and longevity. Recent studies have focused on identifying target substrates for human sirtuin enzymatic activity, but little is known about processes that directly regulate their function. Here, we demonstrate that SIRT2 is phosphorylated both in vitro and in vivo on serine 368 by the cell-cycle regulator, cyclin-dependent kinase 1, and dephosphorylated by the phosphatases CDC14A and CDC14B. Overexpression of SIRT2 mediates a delay in cellular proliferation that is dependent on serine 368 phosphorylation. Furthermore, mutation of serine 368 reduces hyperploidy in cells under mitotic stress due to microtubule poisons.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California San Francisco, California 94158, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: North
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
mesh_terms: D017209:Apoptosis / Q000235:genetics; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D054637:Dual-Specificity Phosphatases; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011123:Polyploidy; D011499:Protein Processing, Post-Translational / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D056565:Sirtuin 2; D037761:Sirtuins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D016203:CDC2 Protein Kinase; D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; C474200:CDC14B protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins