The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase

Brian J. North, Brett L. Marshall, Margie T. Borra, John M. Denu, Eric Verdin

Research output: Contribution to journalArticlepeer-review

1131 Scopus citations

Abstract

The silent information regulator 2 protein (Sir2p) of Saccharomyces cerevisiae is an NAD-dependent histone deacetylase that plays a critical role in transcriptional silencing. Here, we report that a human ortholog of Sir2p, sirtuin type 2 (SIRT2), is a predominantly cytoplasmic protein that colocalizes with microtubules. SIRT2 deacetylates lysine-40 of α-tubulin both in vitro and in vivo. Knockdown of SIRT2 via siRNA results in tubulin hyperacetylation. SIRT2 colocalizes and interacts in vivo with HDAC6, another tubulin deacetylase. Enzymatic analysis of recombinant SIRT2 in comparison to a yeast homolog of Sir2 protein (Hst2p) shows a striking preference of SIRT2 for acetylated tubulin peptide as a substrate relative to acetylated histone H3 peptide. These observations establish SIRT2 as a bona fide tubulin deacetylase.

Original languageEnglish (US)
Pages (from-to)437-444
Number of pages8
JournalMolecular Cell
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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