Mitotic regulation of SIRT2 by cyclin-dependent kinase 1-dependent phosphorylation

Brian J. North, Eric Verdin

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19546-19555
Number of pages10
JournalJournal of Biological Chemistry
Volume282
Issue number27
DOIs
StatePublished - Jul 6 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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