SIRT6, a protein with many faces

Abstract

Sirtuins are NAD(+) dependent deacylases enzymes. There are seven mammalian sirtuins, SIRT1-SIRT7, which are localized to different cellular compartments and are capable of diverse catalytic activities. SIRT6 is a key regulator of healthy ageing. In the past decade our understanding of SIRT6 significantly increased in many different aspects. We know its cellular localization, catalytic activities, substrates and the pathways it is involved in. This review discusses the recent discoveries regarding the SIRT6 enzyme.

Mitochondrial responsibility in ageing process: innocent, suspect or guilty

“…SIRT6 is considered a key regulator of healthy aging (Gertler and Cohen 2013). SIRT6 is recruited to double strand breaks sites in the DNA and stimulates its reparation by stimulating poly-ADP-rybosilase activity of PARP-1 (Mao et al 2011).…”

SnapShot: Mammalian Sirtuins

“…SIRT6 can also remove long-chain acyl groups from peptides in vitro, which is more efficient than its deacetylase activity against peptides derived from H3K9 (Gertler and Cohen, 2013). The long-chain deacylase activity for SIRT6 modulates tumor necrosis factor α (TNFα) by controlling its secretion rate (Jiang et al, 2013).…”

“…SIRT6 promotes genomic stability and helps to maintain telomere integrity. Remarkably, SIRT6 overexpression in male mice increased lifespan by ~15% (Gertler and Cohen, 2013). In addition, SIRT6 protects against several age-related diseases, including cancer and diabetes.…”

JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks

“…SIRT6 is required for the maintenance of genomic stability, as SIRT6 deficiency results in severe genomic instability, sensitivity to DNA damage, and premature aging in mice (Mostoslavsky et al, 2006). SIRT6 catalyzes both deacetylation and mono-ADP ribosylation (Gertler and Cohen, 2013), and it also can remove long-chain fatty acyl moieties from lysine residues (Jiang et al, 2013). The first identified deacetylation substrates of SIRT6 are histone H3 lysines 9 and 56 (Michishita et al, 2008; Yang et al, 2009).…”