SIRT2 regulates nuclear envelope reassembly through ANKLE2 deacetylation.

Tanja Kaufmann,Eva Kukolj,Andreas Brachner,Graham Warren,Karl Mechtler,Sebastian Kostrhon,Dea Slade,Melania Bruno,Susanne Opravil,Etienne Beltzung,Otto Hudecz

doi:10.1242/jcs.192633

Tanja Kaufmann, Eva Kukolj + Show 9 more

Open Access

https://doi.org/10.1242/jcs.192633

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Abstract

ABSTRACTSirtuin 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.

Highlights

Sirtuins are NAD-dependent deacylases and mono(ADP-ribosyl) transferases involved in the regulation of gene silencing, genome stability, cellular metabolism, autophagy, apoptosis and lifespan (Bosch-Presegué and Vaquero, 2015; Choi and Mostoslavsky, 2014)
These results suggest that any perturbation in acetylation homeostasis regulated by Sirtuin 2 (SIRT2) results in nuclear envelope shape defects
SIRT2-depleted cells exhibit reduced proliferation and centrosome amplification, which has been linked with the SIRT2-mediated regulation of the anaphase-promoting complex (APC) (Kim et al, 2011)

Summary

Introduction

Sirtuins are NAD-dependent deacylases and mono(ADP-ribosyl) transferases involved in the regulation of gene silencing, genome stability, cellular metabolism, autophagy, apoptosis and lifespan (Bosch-Presegué and Vaquero, 2015; Choi and Mostoslavsky, 2014). By acting on both histone and non-histone substrates, sirtuins tune protein expression levels and protein activity in accordance with the cellular energy status (Houtkooper et al, 2012). Sirtuins catalyse the transfer of acetyl or acyl groups from lysine residues of substrate proteins onto the ADP-ribose moiety of NAD (Feldman et al, 2012). SIRT2 colocalizes with the microtubule network, D.S., 0000-0002-0052-5910

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