SIRT6

Summary

Gene Symbol: SIRT6
Description: sirtuin 6
Alias: SIR2L6, NAD-dependent protein deacetylase sirtuin-6, SIR2-like protein 6, regulatory protein SIR2 homolog 6, sir2-related protein type 6, sirtuin type 6
Species: human
Products:     SIRT6

Top Publications

  1. Mao Z, Tian X, Van Meter M, Ke Z, Gorbunova V, Seluanov A. Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence. Proc Natl Acad Sci U S A. 2012;109:11800-5 pubmed publisher
    ..Expression of proteins involved in HR such as Rad51, Rad51C, Rad52, NBS1, and Sirtuin 6 (SIRT6) diminished with cellular senescence...
  2. Kitada M, Kume S, Takeda Watanabe A, Kanasaki K, Koya D. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2013;124:153-64 pubmed publisher
    ..Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules...
  3. Michishita E, McCord R, Berber E, Kioi M, Padilla Nash H, Damian M, et al. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature. 2008;452:492-6 pubmed publisher
    ..In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype...
  4. Kawahara T, Michishita E, Adler A, Damian M, Berber E, Lin M, et al. SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Cell. 2009;136:62-74 pubmed publisher
    ..Deficiency of mammalian SIRT6 leads to shortened life span and an aging-like phenotype in mice, but the underlying molecular mechanisms are ..
  5. Sebastian C, Zwaans B, Silberman D, Gymrek M, Goren A, Zhong L, et al. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell. 2012;151:1185-99 pubmed publisher
    ..Here, we identify SIRT6 as a tumor suppressor that regulates aerobic glycolysis in cancer cells...
  6. Michishita E, McCord R, Boxer L, Barber M, Hong T, Gozani O, et al. Cell cycle-dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle. 2009;8:2664-6 pubmed
  7. Lappas M. Anti-inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells. Mediators Inflamm. 2012;2012:597514 pubmed publisher
    ..The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known...
  8. Ronnebaum S, Wu Y, McDonough H, Patterson C. The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical ubiquitination. Mol Cell Biol. 2013;33:4461-72 pubmed publisher
    ..a mechanism for CHIP's influence on longevity by demonstrating that CHIP stabilizes the sirtuin family member SirT6, a lysine deacetylase/ADP ribosylase involved in DNA repair, metabolism, and longevity...
  9. Kugel S, Mostoslavsky R. Chromatin and beyond: the multitasking roles for SIRT6. Trends Biochem Sci. 2014;39:72-81 pubmed publisher
    In recent years there has been a large expansion in our understanding of SIRT6 biology including its structure, regulation, biochemical activity, and biological roles...

More Information

Publications104 found, 100 shown here

  1. Minagawa S, Araya J, Numata T, Nojiri S, Hara H, Yumino Y, et al. Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-?-induced senescence of human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011;300:L391-401 pubmed publisher
    ..Among the sirtuin (SIRT) family, SIRT6, a class III histone deacetylase, has been demonstrated to antagonize senescence...
  2. Kanfi Y, Shalman R, Peshti V, Pilosof S, Gozlan Y, Pearson K, et al. Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett. 2008;582:543-8 pubmed publisher
    ..We show here that levels of the mammalian sirtuin, SIRT6, increased upon nutrient deprivation in cultured cells, in mice after fasting, and in rats fed a calorie-..
  3. Pan P, Feldman J, Devries M, Dong A, Edwards A, Denu J. Structure and biochemical functions of SIRT6. J Biol Chem. 2011;286:14575-87 pubmed publisher
    b>SIRT6 is a member of the evolutionarily conserved sirtuin family of NAD(+)-dependent protein deacetylases and functions in genomic stability and transcriptional control of glucose metabolism...
  4. Mao Z, Hine C, Tian X, Van Meter M, Au M, Vaidya A, et al. SIRT6 promotes DNA repair under stress by activating PARP1. Science. 2011;332:1443-6 pubmed publisher
    Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability...
  5. Frye R. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun. 2000;273:793-8 pubmed
    Sirtuins (Sir2-like proteins) are present in prokaryotes and eukaryotes. Here, two new human sirtuins (SIRT6 and SIRT7) are found to be similar to a particular subset of insect, nematode, plant, and protozoan sirtuins...
  6. Grimley R, Polyakova O, Vamathevan J, McKenary J, Hayes B, Patel C, et al. Over expression of wild type or a catalytically dead mutant of Sirtuin 6 does not influence NF?B responses. PLoS ONE. 2012;7:e39847 pubmed publisher
    b>SIRT6 is involved in inflammation, aging and metabolism potentially by modulating the functions of both NF?B and HIF1?...
  7. Cardus A, Uryga A, Walters G, Erusalimsky J. SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc Res. 2013;97:571-9 pubmed publisher
    ..The aim of this study was to investigate whether SIRT6, a member of the sirtuin family of NAD(+)-dependent protein deacetylases/ADP-ribosyltransferases, protects ..
  8. Michishita E, Park J, Burneskis J, Barrett J, Horikawa I. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell. 2005;16:4623-35 pubmed
    ..We found that: 1) three nuclear SIRT proteins (SIRT1, SIRT6, and SIRT7) show different subnuclear localizations: SIRT6 and SIRT7 are associated with heterochromatic regions ..
  9. McCord R, Michishita E, Hong T, Berber E, Boxer L, Kusumoto R, et al. SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (Albany NY). 2009;1:109-21 pubmed
    ..The mammalian Sir2 family member SIRT6 has been proposed to have analogous functions, because SIRT6-deficiency leads to shortened life span and an aging-..
  10. Feldman J, Baeza J, Denu J. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J Biol Chem. 2013;288:31350-6 pubmed publisher
    ..b>SIRT6 was recently reported to preferentially hydrolyze long-chain fatty acyl groups over acetyl groups...
  11. Tatone C, Di Emidio G, Barbonetti A, Carta G, Luciano A, Falone S, et al. Sirtuins in gamete biology and reproductive physiology: emerging roles and therapeutic potential in female and male infertility. Hum Reprod Update. 2018;24:267-289 pubmed publisher
    ..Biochemical modulation of Sirtuin activity has led to discoveries of the roles of SIRT1, SIRT2, SIRT3 and SIRT6 in improving the competence of oocytes grown or matured in vitro in humans and animal models...
  12. Winnik S, Auwerx J, Sinclair D, Matter C. Protective effects of sirtuins in cardiovascular diseases: from bench to bedside. Eur Heart J. 2015;36:3404-12 pubmed publisher
    ..This review focuses on the cardiovascular effects of Sirt1, Sirt3, Sirt6, and Sirt7. Most is known about Sirt1...
  13. Ribeiro Júnior G, de Souza Xavier Costa N, Belotti L, Dos Santos Alemany A, Amato Lourenço L, da Cunha P, et al. Diesel exhaust exposure intensifies inflammatory and structural changes associated with lung aging in mice. Ecotoxicol Environ Saf. 2019;170:314-323 pubmed publisher
    ..enzyme activity was evaluated by spectrophotometry, sirtuin 1 (SIRT1), sirtuin 2 (SIRT2) and sirtuin 6 (SIRT6) expression was assessed by reverse transcription polymerase chain reaction (RT-PCR), and levels of the sirtuin ..
  14. Matsushima S, Sadoshima J. The role of sirtuins in cardiac disease. Am J Physiol Heart Circ Physiol. 2015;309:H1375-89 pubmed publisher
    ..In addition, Sirt3 protects cardiomyocytes from aging and oxidative stress and suppresses cardiac hypertrophy. Sirt6 has also recently been demonstrated to attenuate cardiac hypertrophy, and Sirt7 is known to regulate apoptosis and ..
  15. Salminen A, Kauppinen A, Kaarniranta K. AMPK/Snf1 signaling regulates histone acetylation: Impact on gene expression and epigenetic functions. Cell Signal. 2016;28:887-95 pubmed publisher
    ..NAD(+) is a substrate for nuclear sirtuins, especially for SIRT1 and SIRT6, which deacetylate histones and transcription factors, e.g...
  16. Wencel P, Lukiw W, Strosznajder J, Strosznajder R. Inhibition of Poly(ADP-ribose) Polymerase-1 Enhances Gene Expression of Selected Sirtuins and APP Cleaving Enzymes in Amyloid Beta Cytotoxicity. Mol Neurobiol. 2018;55:4612-4623 pubmed publisher
    ..Concomitantly, PJ-34 enhanced mRNA level of nuclear Sirt1, Sirt6, mitochondrial Sirt4, and Parp3 in PC12 cells subjected to AβOs toxicity...
  17. Rouble A, Storey K. Characterization of the SIRT family of NAD+-dependent protein deacetylases in the context of a mammalian model of hibernation, the thirteen-lined ground squirrel. Cryobiology. 2015;71:334-43 pubmed publisher
    ..To assess this possibility, protein levels of the seven mammalian SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7), total SIRT activity, and the acetylation status of two downstream SIRT targets (SOD2K68 and NF-κB ..
  18. Mao Q, Gong X, Zhou C, Tu Z, Zhao L, Wang L, et al. Up-regulation of SIRT6 in the hippocampus induced rats with depression-like behavior via the block Akt/GSK3? signaling pathway. Behav Brain Res. 2017;323:38-46 pubmed publisher
    ..the results showed depressive-like behaviors: like body weight, forced swim test and sucrose preference test and SIRT6 was a significant increase in the hippocampal of CUMS rats...
  19. Jesko H, Wencel P, Strosznajder R, Strosznajder J. Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders. Neurochem Res. 2017;42:876-890 pubmed publisher
    ..It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively...
  20. Okun E, Marton D, Cohen D, Griffioen K, Kanfi Y, Illouz T, et al. Sirt6 alters adult hippocampal neurogenesis. PLoS ONE. 2017;12:e0179681 pubmed publisher
    ..b>SIRT6, a member of the sirtuin family, regulates the process of normal aging and increases the lifespan of male mice ..
  21. Cattelan A, Ceolotto G, Bova S, Albiero M, Kuppusamy M, De Martin S, et al. NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusion-induced apoptosis. Vascul Pharmacol. 2015;70:35-44 pubmed publisher
    ..apoptosis; the cleavage of caspase 3, induced a transient upregulation of SIRT1 and downregulation of SIRT6 expression, but decreased SIRT1 activity and reduced NAD(+) content...
  22. Zhao Y, Guan Y, Zhou X, Li G, Li Z, Zhou C, et al. Regenerative Neurogenesis After Ischemic Stroke Promoted by Nicotinamide Phosphoribosyltransferase-Nicotinamide Adenine Dinucleotide Cascade. Stroke. 2015;46:1966-74 pubmed publisher
    ..1 (SIRT1) and SIRT2 inhibited the progrowth action of Nampt-NAD axis, whereas knockdown of SIRT1, SIRT2, and SIRT6 compromised the prodifferentiation effect of Nampt-NAD axis...
  23. Kida Y, Goligorsky M. Sirtuins, Cell Senescence, and Vascular Aging. Can J Cardiol. 2016;32:634-41 pubmed publisher
    ..SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear...
  24. Wyman A, Noor Z, Fishelevich R, Lockatell V, Shah N, Todd N, et al. Sirtuin 7 is decreased in pulmonary fibrosis and regulates the fibrotic phenotype of lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2017;312:L945-L958 pubmed publisher
    ..Sirtuins (SIRTs), particularly SIRT1, SIRT3, and SIRT6, are well-known mediators of aging; however, limited data exist on the contribution of sirtuins to lung fibrosis...
  25. Wu M, Seto E, Zhang J. E2F1 enhances glycolysis through suppressing Sirt6 transcription in cancer cells. Oncotarget. 2015;6:11252-63 pubmed
    ..b>Sirt6, a class III histone deacetylase, has been shown to down regulate glycolysis by inhibiting the expression of ..
  26. Van Meter M, Simon M, Tombline G, May A, Morello T, Hubbard B, et al. JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks. Cell Rep. 2016;16:2641-2650 pubmed publisher
    ..The longevity gene, sirtuin 6 (SIRT6), promotes genome stability by facilitating DNA repair, especially under oxidative stress conditions...
  27. Zhang H, Lu Y, Zhao Y, Zhou D. OsSRT1 is involved in rice seed development through regulation of starch metabolism gene expression. Plant Sci. 2016;248:28-36 pubmed publisher
    OsSRT1 is a NAD(+)-dependent histone deacetylase, closely related to the human SIRT6 that plays key roles in genome stability and metabolic homeostasis. In this work, we investigated the role of OsSRT1 in rice seed development...
  28. Aguilar Arnal L, Ranjit S, Stringari C, Orozco Solis R, Gratton E, Sassone Corsi P. Spatial dynamics of SIRT1 and the subnuclear distribution of NADH species. Proc Natl Acad Sci U S A. 2016;113:12715-12720 pubmed publisher
    ..Importantly, SIRT6, a chromatin-bound deacetylase of the same class, does not influence NADH nuclear localization...
  29. Samant S, Kanwal A, Pillai V, Bao R, Gupta M. The histone deacetylase SIRT6 blocks myostatin expression and development of muscle atrophy. Sci Rep. 2017;7:11877 pubmed publisher
    ..Molecular basis of this metabolic syndrome is not yet completely understood. SIRT6 is a chromatin-bound member of the sirtuin family, implicated in regulating many cellular processes, ranging from ..
  30. Chen J, Xie J, Jin M, Gu Y, Wu C, Guo W, et al. Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration. Cell Death Dis. 2018;9:56 pubmed publisher
    ..Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease...
  31. Lall S. No SIRT6. Nat Struct Mol Biol. 2008;15:336 pubmed publisher
  32. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, et al. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature. 2013;496:110-3 pubmed publisher
    ..Here we show that human SIRT6 efficiently removes long-chain fatty acyl groups, such as myristoyl, from lysine residues...
  33. Tasselli L, Xi Y, Zheng W, Tennen R, Odrowaz Z, Simeoni F, et al. SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence. Nat Struct Mol Biol. 2016;23:434-40 pubmed publisher
    ..Here, we uncover an essential role of the human SIRT6 enzyme in pericentric transcriptional silencing, and we show that this function protects against mitotic defects, ..
  34. Ka N, Na T, Na H, Lee M, Park H, Hwang S, et al. NR1D1 Recruitment to Sites of DNA Damage Inhibits Repair and Is Associated with Chemosensitivity of Breast Cancer. Cancer Res. 2017;77:2453-2463 pubmed publisher
    ..NR1D1 inhibited recruitment of the components of DNA damage response complex such as SIRT6, pNBS1, and BRCA1 to DNA lesions...
  35. Rahnasto Rilla M, McLoughlin P, Kulikowicz T, Doyle M, Bohr V, Lahtela Kakkonen M, et al. The Identification of a SIRT6 Activator from Brown Algae Fucus distichus. Mar Drugs. 2017;15: pubmed publisher
    ..i>Cytoseira nodacaulis, Alaria esculenta) were tested for their ability to activate SIRT6 resulting in H3K9 deacetylation...
  36. Ardestani P, Liang F. Sub-cellular localization, expression and functions of Sirt6 during the cell cycle in HeLa cells. Nucleus. 2012;3:442-51 pubmed publisher
    Sirtuin 6 (Sirt6), a mammalian Sir2 (silent information regulator-2) ortholog, is an NAD (+) -dependent histone deacetylase that modulates chromatin structure and genomic stability...
  37. Hwang B, Jin J, Gao Y, Shi G, Madabushi A, Yan A, et al. SIRT6 protein deacetylase interacts with MYH DNA glycosylase, APE1 endonuclease, and Rad9-Rad1-Hus1 checkpoint clamp. BMC Mol Biol. 2015;16:12 pubmed publisher
    b>SIRT6, a member of the NAD(+)-dependent histone/protein deacetylase family, regulates genomic stability, metabolism, and lifespan...
  38. Kleszcz R, Paluszczak J, Baer Dubowska W. Targeting aberrant cancer metabolism - The role of sirtuins. Pharmacol Rep. 2015;67:1068-80 pubmed publisher
    ..It was recently demonstrated that SIRT6 is a tumor suppressor that modulates aerobic glycolysis by repressing HIF1 transcription...
  39. Wang X, Wang X, Tong M, Gan L, Chen H, Wu S, et al. SIRT6 protects cardiomyocytes against ischemia/reperfusion injury by augmenting FoxO3α-dependent antioxidant defense mechanisms. Basic Res Cardiol. 2016;111:13 pubmed publisher
    b>SIRT6, a member of the NAD(+)-dependent class III deacetylase sirtuin family, has been revealed to play important roles in promoting cellular resistance against oxidative stress...
  40. Elhanati S, Ben Hamo R, Kanfi Y, Varvak A, Glazz R, Lerrer B, et al. Reciprocal Regulation between SIRT6 and miR-122 Controls Liver Metabolism and Predicts Hepatocarcinoma Prognosis. Cell Rep. 2016;14:234-42 pubmed publisher
    Mice overexpressing the longevity protein SIRT6 or deficient for the liver's most prevalent microRNA miR-122 display a similar set of phenotypes, including improved lipid profile and protection against damage linked to obesity...
  41. Baker J, Vuppusetty C, Colley T, Papaioannou A, Fenwick P, Donnelly L, et al. Oxidative stress dependent microRNA-34a activation via PI3K? reduces the expression of sirtuin-1 and sirtuin-6 in epithelial cells. Sci Rep. 2016;6:35871 pubmed publisher
    Sirtuin-1 (SIRT1) and SIRT6, NAD+-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is characterized by the ..
  42. Ashapkin V, Kutueva L, Vanyushin B. Aging as an Epigenetic Phenomenon. Curr Genomics. 2017;18:385-407 pubmed publisher
    ..Multi-substrate deacetylases SIRT1 and SIRT6 affect aging via locus-specific modulations of chromatin structure and activity of multiple regulatory proteins ..
  43. Wood M, Rymarchyk S, Zheng S, Cen Y. Trichostatin A inhibits deacetylation of histone H3 and p53 by SIRT6. Arch Biochem Biophys. 2018;638:8-17 pubmed publisher
    b>SIRT6 is an epigenetic modification enzyme that regulates gene transcription through its deacetylase activity...
  44. Min L, Ji Y, Bakiri L, Qiu Z, Cen J, Chen X, et al. Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat Cell Biol. 2012;14:1203-11 pubmed publisher
    ..Mechanistically, c-Fos induces SIRT6 transcription, which represses survivin by reducing histone H3K9 acetylation and NF-?B activation...
  45. Zhang X, Khan S, Jiang H, Antonyak M, Chen X, Spiegelman N, et al. Identifying the functional contribution of the defatty-acylase activity of SIRT6. Nat Chem Biol. 2016;12:614-20 pubmed publisher
    Mammalian sirtuin 6 (SIRT6) exhibits many pivotal functions and multiple enzymatic activities, but the contribution of each activity to the various functions is unclear...
  46. Tennen R, Bua D, Wright W, Chua K. SIRT6 is required for maintenance of telomere position effect in human cells. Nat Commun. 2011;2:433 pubmed publisher
    ..Here we show that the Sir2 family member SIRT6 is required for maintenance of TPE in human cells...
  47. Chen X, Hao B, Liu Y, Dai D, Han G, Li Y, et al. The histone deacetylase SIRT6 suppresses the expression of the RNA-binding protein PCBP2 in glioma. Biochem Biophys Res Commun. 2014;446:364-9 pubmed publisher
    ..However, the mechanism by which PCBP2 is regulated in glioma remains elusive. We find that SIRT6, one of the NAD(+)-dependent class III deacetylase SIRTUINs, is down-regulated in human glioma tissues and that ..
  48. Wu M, Dickinson S, Wang X, Zhang J. Expression and function of SIRT6 in muscle invasive urothelial carcinoma of the bladder. Int J Clin Exp Pathol. 2014;7:6504-13 pubmed
    b>SIRT6, a member of the class III histone deacetylase, has been shown to inhibit glycolysis and promote DNA double strand break repairs...
  49. Lerrer B, Gertler A, Cohen H. The complex role of SIRT6 in carcinogenesis. Carcinogenesis. 2016;37:108-18 pubmed publisher
    b>SIRT6, a member of the mammalian sirtuins family, functions as a mono-ADP-ribosyl transferase and NAD(+)-dependent deacylase of both acetyl groups and long-chain fatty acyl groups...
  50. Jeh S, Park J, Lee J, Kim D, Do J, Lee S, et al. Differential expression of the sirtuin family in renal cell carcinoma: Aspects of carcinogenesis and prognostic significance. Urol Oncol. 2017;35:675.e9-675.e15 pubmed publisher
    ..SIRT1, SIRT3, and SIRT6 expression was significantly lower in RCC than in normal tissues (P = 0.001, P = 0.006, and P = 0...
  51. Griñan Ferré C, Puigoriol Illamola D, Palomera Ávalos V, Pérez Cáceres D, Companys Alemany J, Camins A, et al. Environmental Enrichment Modified Epigenetic Mechanisms in SAMP8 Mouse Hippocampus by Reducing Oxidative Stress and Inflammaging and Achieving Neuroprotection. Front Aging Neurosci. 2016;8:241 pubmed
    ..Hdac1. Hdac2. Sirt2, and Sirt6. Subsequently, we assessed the effects of EE on neuroprotection-related transcription factors, such as the ..
  52. Ioris R, Galié M, Ramadori G, Anderson J, Charollais A, Konstantinidou G, et al. SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity. Cell Rep. 2017;18:1858-1868 pubmed publisher
    ..traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6)...
  53. Zhang X, Spiegelman N, Nelson O, Jing H, Lin H. SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation. elife. 2017;6: pubmed publisher
    ..b>SIRT6, a sirtuin with established tumor suppressor function, regulates the lysine fatty acylation of R-Ras2...
  54. Mohamad Nasir N, Zainuddin A, Shamsuddin S. Emerging Roles of Sirtuin 6 in Alzheimer's Disease. J Mol Neurosci. 2018;64:157-161 pubmed publisher
    ..Keeping that in mind, this review aims to highlight the possible roles of sirtuin 6 in AD manifestation. ..
  55. Choe M, Brusgard J, Chumsri S, Bhandary L, Zhao X, Lu S, et al. The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells. J Cell Biochem. 2015;116:2210-26 pubmed publisher
    ..The NAD-dependent histone deacetylase, SIRT6, a known tumor suppressor, was a critical regulator of these RUNX2-mediated metabolic changes...
  56. Rahnasto Rilla M, Lahtela Kakkonen M, Moaddel R. Sirtuin 6 (SIRT6) Activity Assays. Methods Mol Biol. 2016;1436:259-69 pubmed publisher
    b>SIRT6 has been shown to possess weak deacetylation, mono-ADP-ribosyltransferase activity, and deacylation activity in vitro. SIRT6 selectively deacetylates H3K9Ac and H3K56Ac...
  57. Ming M, Han W, Zhao B, Sundaresan N, Deng C, Gupta M, et al. SIRT6 promotes COX-2 expression and acts as an oncogene in skin cancer. Cancer Res. 2014;74:5925-33 pubmed publisher
    b>SIRT6 is a SIR2 family member that regulates multiple molecular pathways involved in metabolism, genomic stability, and aging. It has been proposed previously that SIRT6 is a tumor suppressor in cancer...
  58. Zhang P, Liu Y, Wang Y, Zhang M, Lv L, Zhang X, et al. SIRT6 promotes osteogenic differentiation of mesenchymal stem cells through BMP signaling. Sci Rep. 2017;7:10229 pubmed publisher
    b>SIRT6 has been identified as an H3K9 deacetylase and a critical regulator of genome stability, telomere integrity, and metabolic homeostasis...
  59. Baohua Y, Li L. Effects of SIRT6 silencing on collagen metabolism in human dermal fibroblasts. Cell Biol Int. 2012;36:105-8 pubmed publisher
    b>SIRT6 (sirtuin 6) has been identified as an anti-aging protein, and SIRT6-deficient mice display numerous progeroid and aging-like phenotypes. However, there are no reports correlating skin aging with SIRT6...
  60. Lee N, Kim D, Kim E, Park S, Kwon J, Shin J, et al. Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging. Proteomics. 2014;14:1610-22 pubmed publisher
    ..Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive...
  61. Kugel S, Feldman J, Klein M, Silberman D, Sebastian C, Mermel C, et al. Identification of and Molecular Basis for SIRT6 Loss-of-Function Point Mutations in Cancer. Cell Rep. 2015;13:479-488 pubmed publisher
    ..We have previously identified the histone deacetylase SIRT6 as a key tumor suppressor, yet whether point mutations are selected for in cancer remains unclear...
  62. Rasheed H, El Komy M, Hegazy R, Gawdat H, AlOrbani A, Shaker O. Expression of sirtuins 1, 6, tumor necrosis factor, and interferon-γ in psoriatic patients. Int J Immunopathol Pharmacol. 2016;29:764-768 pubmed
    ..Their exact role has not been explained. This study aimed to assess the expression of SIRT1, SIRT6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in psoriatic patients...
  63. Feng X, Luo J, Liu M, Yan W, Zhou Z, Xia Y, et al. Sirtuin 6 promotes transforming growth factor-β1/H2O2/HOCl-mediated enhancement of hepatocellular carcinoma cell tumorigenicity by suppressing cellular senescence. Cancer Sci. 2015;106:559-66 pubmed publisher
    Sirtuin 6 (SIRT6) can function as a tumor suppressor by suppressing aerobic glycolysis and apoptosis resistance...
  64. Zhang J, Liu H, Pan H, Yang Y, Huang G, Yang Y, et al. The histone acetyltransferase hMOF suppresses hepatocellular carcinoma growth. Biochem Biophys Res Commun. 2014;452:575-80 pubmed publisher
    ..Mechanically, we show that hMOF regulates the expression of SIRT6 and its downstream genes...
  65. Shen X, Li P, Xu Y, Chen X, Sun H, Zhao Y, et al. Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer. Oncotarget. 2017;8:74359-74370 pubmed publisher
    ..The results suggested that SIRT4, SIRT6, and SIRT7 were associated with Lauren classification and SIRT3-5 were associated with pStage in gastric cancer...
  66. Liu Y, Xie Q, Wang B, Shao J, Zhang T, Liu T, et al. Inhibition of SIRT6 in prostate cancer reduces cell viability and increases sensitivity to chemotherapeutics. Protein Cell. 2013;4:702-10 pubmed publisher
    b>SIRT6 is an important histone modifying protein that regulates DNA repair, telomere maintenance, energy metabolism, and target gene expression...
  67. Damonte P, Sociali G, Parenti M, Soncini D, Bauer I, Boero S, et al. SIRT6 inhibitors with salicylate-like structure show immunosuppressive and chemosensitizing effects. Bioorg Med Chem. 2017;25:5849-5858 pubmed publisher
    The NAD+-dependent deacetylase SIRT6 is an emerging cancer drug target, whose inhibition sensitizes cancer cells to chemo-radiotherapy and has pro-differentiating effects...
  68. Treviño Saldaña N, García Rivas G. Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals. Oxid Med Cell Longev. 2017;2017:1750306 pubmed publisher
    ..In addition, decreased expression and activity of the deacetylases Sirt1, Sirt3, and Sirt6 have been linked to the development and progression of cardiac dysfunction...
  69. Shun C, Lin S, Hong C, Lin C, Liu C. Sirtuin 6 modulates hypoxia-induced autophagy in nasal polyp fibroblasts via inhibition of glycolysis. Am J Rhinol Allergy. 2016;30:179-85 pubmed publisher
    ..between hypoxia-induced autophagy and glycolysis in nasal polyp fibroblasts, and the regulatory role of Sirtuin 6 (SIRT6) in the pathogenesis of nasal polyp...
  70. Wang L, Ma L, Pang S, Huang J, Yan B. Sequence Variants of SIRT6 Gene Promoter in Myocardial Infarction. Genet Test Mol Biomarkers. 2016;20:185-90 pubmed publisher
    ..Genetic variants of low and rare frequencies have been proposed as the main causes of CAD. SIRT6, one of the highly conserved NAD-dependent class III deacetylases, has been implicated in cardiovascular diseases...
  71. Joo D, An S, Choi B, Kim K, Choi Y, Ahn K, et al. MicroRNA?378b regulates ??1?type 1 collagen expression via sirtuin 6 interference. Mol Med Rep. 2017;16:8520-8524 pubmed publisher
    ..Sirtuin 6 (SIRT6), a member of the sirtuin family of proteins, regulates collagen metabolism and is an established anti?aging ..
  72. Garcia Peterson L, Ndiaye M, Singh C, Chhabra G, Huang W, Ahmad N. SIRT6 histone deacetylase functions as a potential oncogene in human melanoma. Genes Cancer. 2017;8:701-712 pubmed publisher
    ..This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma...
  73. Bauer I, Grozio A, Lasiglié D, Basile G, Sturla L, Magnone M, et al. The NAD+-dependent histone deacetylase SIRT6 promotes cytokine production and migration in pancreatic cancer cells by regulating Ca2+ responses. J Biol Chem. 2012;287:40924-37 pubmed publisher
    ..Studies show that the sirtuin SIRT6 promotes inflammation by enhancing TNF expression...
  74. Liu M, Liang K, Zhen J, Zhou M, Wang X, Wang Z, et al. Sirt6 deficiency exacerbates podocyte injury and proteinuria through targeting Notch signaling. Nat Commun. 2017;8:413 pubmed publisher
    ..Here, we show that histone deacetylase Sirt6 protects against podocyte injury through epigenetic regulation of Notch signaling...
  75. Wang L, Guo W, Ma J, Dai W, Liu L, Guo S, et al. Aberrant SIRT6 expression contributes to melanoma growth: Role of the autophagy paradox and IGF-AKT signaling. Autophagy. 2018;14:518-533 pubmed publisher
    ..The histone deacetylase SIRT6 (sirtuin 6) is a known autophagy regulator, and its involvement in cancer development has been reported...
  76. Bai L, Lin G, Sun L, Liu Y, Huang X, Cao C, et al. Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway. Oncotarget. 2016;7:40377-40386 pubmed publisher
    Sirtuin6 (SIRT6), a member of the sirtuins protein family, plays multiple complex roles in cancer...
  77. Zhao G, Wang H, Xu C, Wang P, Chen J, Wang P, et al. SIRT6 delays cellular senescence by promoting p27Kip1 ubiquitin-proteasome degradation. Aging (Albany NY). 2016;8:2308-2323 pubmed publisher
    Sirtuin6(SIRT6) has been implicated as a key factor in aging and aging-related diseases. However, the role of SIRT6 in cellular senescence has not been fully understood...
  78. Penrose H, Heller S, Cable C, Makboul R, Chadalawada G, Chen Y, et al. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6. Biochem Biophys Res Commun. 2016;469:370-6 pubmed publisher
    ..In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that ..
  79. Yang J, Gupta V, Carroll K, Liebler D. Site-specific mapping and quantification of protein S-sulphenylation in cells. Nat Commun. 2014;5:4776 pubmed publisher
    ..novel redox mechanisms, including S-sulphenyl-mediated redox regulation of the transcription factor HIF1A by SIRT6. S-sulphenylation is favored at solvent-exposed protein surfaces and is associated with sequence motifs that are ..
  80. Lu C, Hsu C, Lin P, Lai C, Lin H, Yang C, et al. The potential of SIRT6 and SIRT7 as circulating markers for head and neck squamous cell carcinoma. Anticancer Res. 2014;34:7137-43 pubmed
    ..In the cancer group, the expression level of SIRT1 was down-regulated (p<0.05); in contrast, SIRT6 and SIRT7 were significantly up-regulated (p<0.001)...
  81. Liu R, Liu H, Ha Y, Tilton R, Zhang W. Oxidative stress induces endothelial cell senescence via downregulation of Sirt6. Biomed Res Int. 2014;2014:902842 pubmed publisher
    ..We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging ..
  82. Yao L, Cui X, Chen Q, Yang X, Fang F, Zhang J, et al. Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat. Cell Rep. 2017;20:641-654 pubmed publisher
    Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a ?-adrenergic agonist...
  83. Bhardwaj A, Das S. SIRT6 deacetylates PKM2 to suppress its nuclear localization and oncogenic functions. Proc Natl Acad Sci U S A. 2016;113:E538-47 pubmed publisher
    b>SIRT6 (sirtuin 6) is a member of sirtuin family of deacetylases involved in diverse processes including genome stability, metabolic homeostasis, and tumorigenesis...
  84. Mu W, Wang Z, Ma C, Jiang Y, Zhang N, Hu K, et al. Metformin promotes the proliferation and differentiation of murine preosteoblast by regulating the expression of sirt6 and oct4. Pharmacol Res. 2018;129:462-474 pubmed publisher
    ..Furthermore, we have observed that metformin can promote SIRT6 expression before and during differentiation of murine preosteoblast...
  85. Kim K, An S, Choi B, Joo D, Choi Y, Ahn K, et al. Arctiin regulates collagen type 1? chain 1 mRNA expression in human dermal fibroblasts via the miR?378b?SIRT6 axis. Mol Med Rep. 2017;16:9120-9124 pubmed publisher
    ..expression of microRNA?378b (miR?378b), downregulated by arctiin, was correlated with the expression of sirtuin?6 (SIRT6) mRNA, a regulator of COL1A1 mRNA...
  86. Santos Barriopedro I, Bosch Presegué L, Marazuela Duque A, de la Torre C, Colomer C, Vazquez B, et al. SIRT6-dependent cysteine monoubiquitination in the PRE-SET domain of Suv39h1 regulates the NF-κB pathway. Nat Commun. 2018;9:101 pubmed publisher
    Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an ..
  87. Tao N, Ren J, Tang H, Ran L, Zhou H, Liu B, et al. Deacetylation of Ku70 by SIRT6 attenuates Bax-mediated apoptosis in hepatocellular carcinoma. Biochem Biophys Res Commun. 2017;485:713-719 pubmed publisher
    b>SIRT6 is a class III histone deacetylase that has been implicated in HCC development...
  88. Stöhr R, Mavilio M, Marino A, Casagrande V, Kappel B, Möllmann J, et al. ITCH modulates SIRT6 and SREBP2 to influence lipid metabolism and atherosclerosis in ApoE null mice. Sci Rep. 2015;5:9023 pubmed publisher
    ..We found that ITCH ubiquitinates SIRT6, leading to its breakdown, and thus promoting hepatic lipid infiltration through reduced fatty acid oxidation...
  89. Van Meter M, Mao Z, Gorbunova V, Seluanov A. SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells. Cell Cycle. 2011;10:3153-8 pubmed
    Emerging evidence suggests that Sirtuin 6 (SIRT6) functions as a longevity assurance gene by promoting genomic stability, regulating metabolic processes and attenuating inflammation...
  90. Hirvonen K, Laivuori H, Lahti J, Strandberg T, Eriksson J, Hackman P. SIRT6 polymorphism rs117385980 is associated with longevity and healthy aging in Finnish men. BMC Med Genet. 2017;18:41 pubmed publisher
    Sirtuin-6 (SIRT6) is involved in various crucial cellular pathways, being a key regulator of telomere structure, DNA repair, metabolism, transcriptional control and the NF-kappa B pathway...
  91. Cagnetta A, Soncini D, Orecchioni S, Talarico G, Minetto P, Guolo F, et al. Depletion of SIRT6 enzymatic activity increases acute myeloid leukemia cells' vulnerability to DNA-damaging agents. Haematologica. 2018;103:80-90 pubmed publisher
    ..Recent studies demonstrate that SIRT6, a NAD+-dependent nuclear deacetylase, functions as genome-guardian by preserving DNA integrity in ..
  92. Pan H, Guan D, Liu X, Li J, Wang L, Wu J, et al. SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res. 2016;26:190-205 pubmed publisher
    b>SIRT6 belongs to the mammalian homologs of Sir2 histone NAD(+)-dependent deacylase family. In rodents, SIRT6 deficiency leads to aging-associated degeneration of mesodermal tissues...