Sirtuin 6 (SIRT6) (SIRT6)

Sirtuin 6 (SIRT6) is a member of the evolutionarily conserved sirtuin family of NAD+-dependent enzymes, primarily localized in the nucleus where it associates with chromatin [1.1.1, 1.2.1]. It functions as a protein deacetylase, deacylase, and mono-ADP-ribosyltransferase, playing a critical role in maintaining genomic stability through DNA repair (specifically base excision repair and non-homologous end joining) and telomere maintenance [1.3.2, 1.3.4]. SIRT6 is a key regulator of glucose and lipid metabolism, acting as a co-repressor of transcription factors like NF-κB and HIF-1α to suppress inflammation and glycolysis [1.2.4, 1.4.4]. In human health, SIRT6 is frequently described as a longevity protein due to its ability to counteract aging-related processes; however, its role in cancer is complex and context-specific, acting as either a tumor suppressor or an oncogene [1.1.2, 1.2.1]. Pharmacological modulation of SIRT6 is an active area of research, with small-molecule activators like UBCS039 and MDL-801 being explored for their potential to treat metabolic disorders and extend lifespan, while inhibitors are investigated for specific cancer types [1.4.3, 1.5.4].

Other names

NAD-dependent protein deacetylase sirtuin-6SIR2L6Mono-ADP-ribosyltransferase sirtuin-6SIR2-like protein 6Regulatory protein SIR2 homolog 6NAD-dependent protein deacylase sirtuin-6

SIRT6 modulators act by either allosterically activating the enzyme's deacetylase activity (e.g., UBCS039, MDL-801) or by inhibiting the catalytic site to block its enzymatic functions [1.5.3, 1.5.4].