2020
DOI: 10.1002/med.21753
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Abstract: The biological functions of sirtuin 6 (SIRT6; e.g., deacetylation, defatty‐acylation, and mono‐ADP‐ribosylation) play a pivotal role in regulating lifespan and several fundamental processes controlling aging such as DNA repair, gene expression, and telomeric maintenance. Over the past decades, the aberration of SIRT6 has been extensively observed in diverse life‐threatening human diseases. In this comprehensive review, we summarize the critical roles of SIRT6 in the onset and progression of human diseases incl… Show more

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Cited by 75 publications
(48 citation statements)
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References 322 publications
(491 reference statements)
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“…The discovery of allosteric modulators targeting SIRT6 has long been challenging 29 , 35 . Herein, the reversed allosteric strategy AlloReverse and the related hybrid pipeline developed by our lab were exploited to identify potential allosteric pockets in SIRT6 for further structure-based rational drug design (Supporting Information Fig.…”
Section: Resultsmentioning
confidence: 99%
“…The discovery of allosteric modulators targeting SIRT6 has long been challenging 29 , 35 . Herein, the reversed allosteric strategy AlloReverse and the related hybrid pipeline developed by our lab were exploited to identify potential allosteric pockets in SIRT6 for further structure-based rational drug design (Supporting Information Fig.…”
Section: Resultsmentioning
confidence: 99%
“…SIRT6 can effectively remove the acetyl groups from H3K9, H3K18, and H3K27, whereas its deacetylation activity is weak on H3K4ac, H3K14ac, H3K23ac, H3K36ac, H3K56ac, and H3K79ac ( 37 ). In addition to histones, the substrates of SIRT6 include acetylated lysine residues of other proteins, including GCN5 K549ac, PKM2 K433ac, Ku70 K542ac, NAMPT K53ac/369ac, XBP1s K257/297ac, SOD2 K68/122ac, and p53 K382ac ( 2 ). The catalytic mechanism of SIRT6-mediated enzymatic function has been well reviewed by Fiorentino et al.…”
Section: Enzymatic Characteristics Of Sirt6mentioning
confidence: 99%
“…First, SIRT6 is categorized as a class III histone deacetylase with deacetylation activity ( 1 ). However, its substrates are not limited to the acetyl groups of histone H3 and H4 lysine residues but can also include other proteins with acetyl groups on their lysine residues ( 2 ), allowing SIRT6 to regulate gene expression or protein activity through post-translational modifications (PTMs). Second, SIRT6 has defatty-acylation activity, which enables it to regulate the secretion of proteins including tumor necrosis factor alpha (TNF-α) ( 3 ).…”
Section: Introductionmentioning
confidence: 99%
“…SIRT6, a nuclear protein and a special member of the sirtuin family, has the activity of ADP-ribosyl transferase and NAD + -dependent deacetylase and is involved in multiple biological functions including life span, inflammation, metabolism, and cancer. Increasing studies have confirmed the beneficial role of SIRT6 in inflammatory diseases ( Liu G. et al, 2021 ). Therefore, SIRT6 might have a role in regulatory mechanisms of the inflammatory process, which participate in the progress of ALF.…”
Section: Introductionmentioning
confidence: 97%