SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation

J Cell Sci. 2016 Dec 15;129(24):4607-4621. doi: 10.1242/jcs.192633. Epub 2016 Nov 14.

Abstract

Sirtuin 2 (SIRT2) is an NAD-dependent deacetylase known to regulate microtubule dynamics and cell cycle progression. SIRT2 has also been implicated in the pathology of cancer, neurodegenerative diseases and progeria. Here, we show that SIRT2 depletion or overexpression causes nuclear envelope reassembly defects. We link this phenotype to the recently identified regulator of nuclear envelope reassembly ANKLE2. ANKLE2 acetylation at K302 and phosphorylation at S662 are dynamically regulated throughout the cell cycle by SIRT2 and are essential for normal nuclear envelope reassembly. The function of SIRT2 therefore extends beyond the regulation of microtubules to include the regulation of nuclear envelope dynamics.

Keywords: ANKLE2; Cell cycle; Nuclear envelope; SIRT2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Biotinylation
  • Cell Cycle
  • Cell Nucleus Shape
  • Chromatography, Affinity
  • HEK293 Cells
  • Humans
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Proteomics
  • Sirtuin 2 / metabolism*

Substances

  • Lem4 protein, human
  • Membrane Proteins
  • Nuclear Proteins
  • Sirtuin 2