| 27824900 | The role of Sirtuin 6 (SIRT6) as a tumor suppressor or oncogene in liver cancer remains controversial |
| 27824900 | In addition, SIRT6 silencing significantly prevented the growth of HCC cell lines by inducing cellular senescence in the p16/Rb- and p53/p21-pathway independent manners |
| 27824900 | SIRT6 knockdown promoted G2/M phase arrest and downregulation of genes encoding histone variants associated with nucleosome assembly, which could be attributed to DNA damage |
| 27101740 | Ergothioneine oxidation in the protection against high-glucose induced endothelial senescence: Involvement of SIRT1 and SIRT6 |
| 27101740 | Notably, the Egt beneficial effect was exerted through the upregulation of sirtuin 1 (SIRT1) and sirtuin 6 (SIRT6) expression and the downregulation of p66Shc and NF-kappaB |
| 27101740 | These data provide the first evidence of the Egt ability to interfere with endothelial senescence linked to hyperglycaemia through the regulation of SIRT1 and SIRT6 signaling, thus further strengthening the already assessed role of these two histone deacetylases in type 2 diabetes |
| 27043296 | SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence |
| 27043296 | 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, genomic instability, and cellular senescence |
| 27043296 | At pericentric heterochromatin, SIRT6 promotes deacetylation of a new substrate, residue K18 of histone H3 (H3K18), and inactivation of SIRT6 in cells leads to H3K18 hyperacetylation and aberrant accumulation of pericentric transcripts |
| 27043296 | Together, our findings reveal a new function for SIRT6 and regulation of acetylated H3K18 at heterochromatin, and demonstrate the pathogenic role of deregulated pericentric transcription in aging- and cancer-related cellular dysfunction |
| 26948035 | SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear |
| 26948035 | Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation |
| 26940461 | Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-kappaB signaling |
| 26940461 | SIRT6 is a member of the sirtuin family of NAD(+)-dependent histone deacetylases, which is responsible for mediating the effects of CR |
| 26940461 | The transcription factor NF-kappaB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6 |
| 26940461 | Here we describe the crucial role of SIRT6 in aging and inflammation |
| 26940461 | We show that CR had improved renal insufficiency and enhanced SIRT6 expression after 6-month treatment in aged mice |
| 26940461 | Culture cells in low glucose (LG) conditions also showed resistance to cell senescence and enhanced SIRT6 expression compared to normal glucose (NG) group, showing beneficial effects of the CR-mimic cultural conditions |
| 26940461 | Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-kappaB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-kappaB signaling |
| 26940461 | These findings confirm the key status of CR and disclose the critical role of SIRT6 on aging and inflammation |
| 26768768 | SIRT6 belongs to the mammalian homologs of Sir2 histone NAD(+)-dependent deacylase family |
| 26768768 | In rodents, SIRT6 deficiency leads to aging-associated degeneration of mesodermal tissues |
| 26768768 | It remains unknown whether human SIRT6 has a direct role in maintaining the homeostasis of mesodermal tissues |
| 26768768 | To this end, we generated SIRT6 knockout human mesenchymal stem cells (hMSCs) by targeted gene editing |
| 26654351 | Knockdown of SIRT6 Enables Human Bone Marrow Mesenchymal Stem Cell Senescence |
| 26654351 | While it has been shown that sirtuin 6 (SIRT6) is an important antiaging factor in various cells, the role of SIRT6 in hBM-MSCs remains unknown |
| 26654351 | The hBM-MSCs from different ages were cultured for quantifying SIRT6 expression by mRNA and Western blotting |
| 26654351 | The knockdown of SIRT6 in hBM-MSCs was used to investigate its impact on aging |
| 26654351 | SIRT6 expression increased with age, while the proliferative and migration abilities of aged hBM-MSCs were decreased compared with young cells |
| 26654351 | Knockdown of SIRT6 impaired the proliferative, migration, and oxidative stress resistance potentials of BM-MSCs |
| 26654351 | Aging results in compensatory overexpression of SIRT6 in hBM-MSCs |
| 26654351 | Downregulation of SIRT6 in these cells resulted in less cell proliferation and migration but increased SA-beta-Gal activity and p16 expression |
| 26654351 | These results suggest that SIRT6 regulates the aging process in hBM-MSCs and could serve as a target for their rejuvenation |
| 26639398 | The aim of our study was to evaluate if Sirt6, a NAD + dependent histone deacetylase, plays a protective role in cartilage degeneration by suppressing cellular senescence and inflammatory responses |
| 26639398 | These data strongly suggest that overexpression of Sirt6 can prevent OA development by reducing both the inflammatory response and chondrocytes senescence |
| 26639398 | Therefore, the development of specific activators of Sirt6 may have therapeutic potential for the treatment of OA |
| 26191269 | SIRT6/NF-kappaB signaling axis in ginsenoside Rg1-delayed hematopoietic stem/progenitor cell senescence |
| 26191269 | OBJECTIVE: To investigate the role of SIRT6/NF-kappaB signaling axis in ginsenoside Rg1-delayed hematopoietic stem/progenitor cell senescence and to provide theoretical and experimental evidence for delaying HSC/HPC senescence pathway |
| 26191269 | Quantitative PCR and Western blotting were used to detect the mRNA and protein expression of senescence regulatory molecules, such as SIRT6 and NF-kappaB |
| 26191269 | RESULTS: Compared with the aging group, the positive rate of SA-beta-gal staining cells and the proportion of cells in G1 phase decreased; the number of CFU-Mix increased; mRNA and protein expression of SIRT6 increased; mRNA and protein expression of NF-kappaB was down-regulated in Rg1 delaying and treatment groups; the changes of the indicators in Rg1 delaying group were more significant than those in Rg1 treatment group |
| 26112889 | This review focuses on the cardiovascular effects of Sirt1, Sirt3, Sirt6, and Sirt7 |
| 26112889 | Sirt6 is implicated in ameliorating dyslipidaemia, cellular senescence, and left ventricular hypertrophy |
| 26084179 | OBJECTIVE: To investigate the effect of SIRT6/NF-kappaB signal axis in delaying hematopoietic stem/progenitor cell senescence with ginsenoside Rg1, in order to provide theatrical and experimental basis for looking for methods for delaying HSC senescence |
| 26084179 | The mRNA and protein of senescence regulation molecules SIRT6 and NF-KB were examined by realtime fluorescence quantitative PCR (FQ-PCR) and western blotting |
| 26084179 | RESULT: Compared with the senescence group, the Rg1 anti-senescence group and the Rg1-treated group showed lower percentage in SA-beta-Gal-stained positive cells, decreased cell proportion in G1 phase, increased number of CFU-Mix, up-regulated in SIRT6 mRNA and protein expression, down-regulation in NF-KB mRNA and protein expression |
| 26084179 | CONCLUSION: Rg, may inhibit Sca-1 + HSC/HPC senescence induced by t-BHP by regulating SIRT6/NF-KB signal path |
| 25819580 | OBJECTIVE: SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, has been implicated as a key factor in aging-related diseases |
| 25819580 | However, the role of SIRT6 in chondrocytes has not been fully explored |
| 25819580 | The purpose of this study was to examine the role of SIRT6 in human chondrocytes by inhibiting SIRT6 in vitro |
| 25819580 | DESIGN: First, the localization of SIRT6 and proliferation cell nuclear antigen (PCNA) in human cartilages was examined by immunohistochemistry |
| 25819580 | Next, SIRT6 was depleted by RNA interference (RNAi), and the effect of SIRT6 depletion on changes in gene expression, protein levels, proliferation, and senescence in human chondrocytes was assessed |
| 25819580 | RESULTS: Immunohistochemical analysis showed SIRT6 was preferentially expressed in the superficial zone chondrocytes and PCNA-positive cluster-forming chondrocytes in the osteoarthritic cartilage tissue samples |
| 25819580 | Real-time PCR analysis showed that matrix metalloproteinase 1 (MMP-1) and MMP-13 mRNA were significantly increased by SIRT6 inhibition |
| 25819580 | Moreover, SIRT6 inhibition significantly reduced proliferation and increased senescence associated beta-galactosidase (SA-beta-Gal)-positive chondrocytes; it also led to increased p16 levels |
| 25819580 | Immunofluorescence microscopy showed that gammaH2AX foci and TIFs were increased by SIRT6 inhibition |
| 25819580 | CONCLUSION: Depletion of SIRT6 in human chondrocytes caused increased DNA damage and telomere dysfunction, and subsequent premature senescence |
| 25819580 | These findings suggest that SIRT6 plays an important role in the regulation of senescence of human chondrocytes |
| 25683165 | Sirtuin 6 promotes transforming growth factor-beta1/H2O2/HOCl-mediated enhancement of hepatocellular carcinoma cell tumorigenicity by suppressing cellular senescence |
| 25683165 | Sirtuin 6 (SIRT6) can function as a tumor suppressor by suppressing aerobic glycolysis and apoptosis resistance |
| 25683165 | Here we report that the upregulation of SIRT6 expression was required for transforming growth factor (TGF)-beta1 and H2O2/HOCl reactive oxygen species (ROS) to promote the tumorigenicity of hepatocellular carcinoma (HCC) cells |
| 25683165 | Transforming growth factor-beta1/H2O2/HOCl could upregulate SIRT6 expression in HCC cells by inducing the sustained activation of ERK and Smad pathways |
| 25683165 | Sirtuin 6 in turn abrogated the inducing effect of TGF-beta1/H2O2/HOCl on cellular senescence of HCC cells, and was required for the ERK pathway to efficiently suppress the expression of p16 and p21 |
| 25683165 | However, SIRT6 was inefficient in antagonizing the promoting effect of TGF-beta1/H2O2 HOCl on aerobic glycolysis and anoikis resistance |
| 25683165 | Intriguingly, if SIRT6 expression was inhibited, the promoting effect of TGF-beta1/H2O2/HOCl on aerobic glycolysis and anoikis resistance was not sufficient to enhance the tumorigenicity of HCC cells |
| 25683165 | Suppressing the upregulation of SIRT6 enabled TGF-beta1/H2O2/HOCl to induce cellular senescence, thereby abrogating the enhancement of HCC cell tumorigenicity by TGF-beta1/H2O2/HOCl |
| 25476852 | Posttranslational modification of Sirt6 activity by peroxynitrite |
| 25476852 | The mammalian sirtuin 6 (Sirt6) is a site-specific histone deacetylase that regulates chromatin structure and many fundamental biological processes |
| 25476852 | The basic molecular mechanisms underlying regulation of Sirt6 enzymatic function are largely unknown |
| 25476852 | Here we hypothesized that Sirt6 function can be regulated via posttranslational modification, focusing on the role of peroxynitrite, one of the major reactive nitrogen species formed by excessive nitric oxide and superoxide generated during disease processes |
| 25476852 | We found that incubation of purified recombinant Sirt6 protein with 3-morpholinosydnonimine (SIN-1; a peroxynitrite donor that generates nitric oxide and superoxide simultaneously) increased Sirt6 tyrosine nitration and decreased its intrinsic catalytic activity |
| 25476852 | Similar results were observed in SIN-1-treated Sirt6, which was overexpressed in HEK293 cells, and in endogenous Sirt6 when human retinal microvascular endothelial cells were treated with SIN-1 |
| 25476852 | To further investigate whether Sirt6 nitration occurs under pathological conditions, we determined Sirt6 nitration and activity in retina using a model of endotoxin-induced retinal inflammation |
| 25476852 | Our data showed that Sirt6 nitration was increased, whereas its activity was decreased, in this model |
| 25476852 | With mass spectrometry, we identified that tyrosine 257 in Sirt6 was nitrated after SIN-1 treatment |
| 25476852 | Mutation of tyrosine 257 to phenylalanine caused loss of Sirt6 activity and abolished SIN-1-induced nitration and decrease in its activity |
| 25476852 | Mass spectrometry analysis also revealed oxidation of methionine and tryptophan in Sirt6 after SIN-1 treatment |
| 25476852 | Our results demonstrate a novel regulatory mechanism controlling Sirt6 activity through reactive nitrogen species-mediated posttranslational modification under oxidative and nitrosative stress |
| 25304127 | SIRT6 is associated with redox state and inhibits cellular senescence and fibrosis |
| 25162034 | Oxidative stress induces endothelial cell senescence via downregulation of Sirt6 |
| 25162034 | We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence |
| 25162034 | Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein |
| 25162034 | The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated beta-galactosidase activity |
| 25162034 | All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2 |
| 25162034 | In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy |
| 24782448 | Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging |
| 24782448 | Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive |
| 24782448 | In the present study, we identified SIRT6- and SIRT7-interacting proteins, and compared their interactomes to investigate functional links |
| 24782448 | Our interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while confirming seven and 111 proteins identified previously for SIRT6 and SIRT7, respectively |
| 24782448 | Comparison of SIRT6 and SIRT7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links |
| 24782448 | Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation |
| 24782448 | NPM1 was found to be deacetylated by both SIRT6 and SIRT7 |
| 24782448 | In senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7, suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in the aging process |
| 24782448 | Our comparative interactomic study of SIRT6 and SIRT7 implies important functional links to aging by their associations with interacting proteins |
| 25946838 | Peptide AED and EDL increase cell proliferation, decreasing expression of marker of aging p16, p21, p53 and increasing expression of SIRT-6 in young and aged renal cell culture |
| 25946838 | The reduction of SIRT-6 synthesis in cell is one of the causes of cell senescence |
| 24367027 | Autophagy induction by SIRT6 through attenuation of insulin-like growth factor signaling is involved in the regulation of human bronchial epithelial cell senescence |
| 24367027 | Cigarette smoke (CS)-induced cellular senescence has been implicated in the pathogenesis of chronic obstructive pulmonary disease, and SIRT6, a histone deacetylase, antagonizes this senescence, presumably through the attenuation of insulin-like growth factor (IGF)-Akt signaling |
| 24367027 | SIRT1, a representative sirtuin family, has been demonstrated to activate autophagy, but a role for SIRT6 in autophagy activation has not been shown |
| 24367027 | Therefore, we sought to investigate the regulatory role for SIRT6 in autophagy activation during CS-induced cellular senescence |
| 24367027 | SIRT6 expression levels were modulated by cDNA and small interfering RNA transfection in human bronchial epithelial cells (HBECs) |
| 24367027 | We demonstrated that SIRT6 expression levels were decreased in lung homogenates from chronic obstructive pulmonary disease patients, and SIRT6 expression levels correlated significantly with the percentage of forced expiratory volume in 1 s/forced vital capacity |
| 24367027 | CS extract (CSE) suppressed SIRT6 expression in HBECs |
| 24367027 | CSE-induced HBEC senescence was inhibited by SIRT6 overexpression, whereas SIRT6 knockdown and mutant SIRT6 (H133Y) without histone deacetylase activity enhanced HBEC senescence |
| 24367027 | SIRT6 overexpression induced autophagy via attenuation of IGF-Akt-mTOR signaling |
| 24367027 | Conversely, SIRT6 knockdown and overexpression of a mutant SIRT6 (H133Y) inhibited autophagy |
| 24367027 | Autophagy inhibition by knockdown of ATG5 and LC3B attenuated the antisenescent effect of SIRT6 overexpression |
| 24367027 | These results suggest that SIRT6 is involved in CSE-induced HBEC senescence via autophagy regulation, which can be attributed to attenuation of IGF-Akt-mTOR signaling |
| 23997094 | Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve |
| 23592245 | Sirtuin 6: a review of biological effects and potential therapeutic properties |
| 23592245 | SIRT6, an enzyme highly expressed in skeletal muscles, brain, heart, liver, and thymus, affects transcriptional regulation in a tissue-specific manner |
| 23592245 | SIRT6 promotes resistance to DNA damage and oxidative stress, the principal defects associated with age-related diseases |
| 23592245 | The modulation of aging and other metabolic functions by SIRT6 may be indicative of previously unrecognized regulatory systems in the cell |
| 23592245 | The propensity of individual SIRT6 molecules to undergo intramolecular mono-ADP-ribosylation, suggests this auto-ribosylation may contribute to the self-regulation of SIRT6 function |
| 23592245 | Until recently, SIRT6 was an orphan enzyme whose catalytic activity and substrates were unclear |
| 23592245 | It was known that, similar to the yeast Sir2 protein, human SIRT6 deacetylates histones and regulates DNA stability and repair; however, new mechanistic insights can be derived from the discovery of the highly substrate-specific histone deacetylase activity of SIRT6 |
| 23592245 | By maintaining both the integrity and the expression of the mammalian genome, SIRT6 may help prevent cellular senescence |
| 23592245 | Moreover, successful molecular modulation of SIRT6 activity may lead to the development of new chemotherapeutic modalities |
| 23592245 | The action of SIRT6 is described in this review, with an emphasis on the cellular roles of the enzyme and the relation of those enzymatic functions to human biology and disease |
| 23201774 | SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence |
| 23201774 | The aim of this study was to investigate whether SIRT6, a member of the sirtuin family of NAD(+)-dependent protein deacetylases/ADP-ribosyltransferases, protects endothelial cells from premature senescence and dysfunction, and if so which is its mode of action |
| 23201774 | METHODS AND RESULTS: mRNA expression analysis demonstrated comparable levels of SIRT1 and SIRT6 transcripts in endothelial cells derived from different vascular beds and significantly higher levels of SIRT6 in these cells relative to those in haematopoietic progenitor cells |
| 23201774 | SIRT6 depletion by RNA interference in human umbilical vein endothelial cells (HUVEC) and aortic endothelial cells reduced cell proliferation, increased the fraction of senescence-associated-beta-galactosidase-positive cells, and diminished the ability of the cells to form tubule networks on Matrigel |
| 23201774 | CONCLUSION: This work demonstrates that the presence of SIRT6 in endothelial cells confers protection from telomere and genomic DNA damage, thus preventing a decrease in replicative capacity and the onset of premature senescence |
| 23201774 | These findings suggest that SIRT6 may be important to maintain endothelial homeostatic functions and delay vascular ageing |
| 22753495 | Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence |
| 22753495 | However, overexpression of SIRT6 in "middle-aged" and presenescent cells strongly stimulated HR repair, and this effect was dependent on mono-ADP ribosylation activity of poly(ADP-ribose) polymerase (PARP1) |
| 22753495 | SIRT6 activation provides a potential therapeutic strategy to prevent the decline in genome maintenance |
| 22149724 | Overexpression of SIRT6 in porcine fetal fibroblasts attenuates cytotoxicity and premature senescence caused by D-galactose and tert-butylhydroperoxide |
| 22149724 | SIRT6, a member of the yeast silent information regulator 2 (SIR2) family, possesses both robust ADP-ribosyltransferase activity and protein deacetylase activity depending on NAD(+) |
| 22149724 | However, the mechanism by which SIRT6 overexpression affects cellular ageing is not well understood |
| 22149724 | In this study, we investigated the effect of SIRT6 overexpression on cytotoxicity and ageing syndromes |
| 22149724 | A full-length cDNA of porcine SIRT6 was inserted into pcDNA3 |
| 22149724 | Overexpression of SIRT6 was identified by quantitative real-time polymerase chain reaction and western blot assay |
| 22149724 | The results showed that SIRT6 overexpression in cells decreased damage to the nuclei |
| 22149724 | Our observations suggested that one function of SIRT6 in PFFs was to dampen cytotoxicity, and, therefore, to decrease the damage that causes premature senescence |
| 21738489 | Dynamic chromatin localization of Sirt6 shapes stress transcriptional networks |
| 21738489 | The sirtuin Sirt6 is a NAD-dependent histone deacetylase that is implicated in gene regulation and lifespan control |
| 21738489 | Sirt6 can interact with the stress-responsive transcription factor NF-kappaB and regulate some NF-kappaB target genes, but the full scope of Sirt6 target genes as well as dynamics of Sirt6 occupancy on chromatin are not known |
| 21738489 | Here we map Sirt6 occupancy on mouse promoters genome-wide and show that Sirt6 occupancy is highly dynamic in response to TNF-alpha |
| 21738489 | More than half of Sirt6 target genes are only revealed upon stress-signaling |
| 21738489 | The majority of genes bound by NF-kappaB subunit RelA recruit Sirt6, and dynamic Sirt6 relocalization is largely driven in a RelA-dependent manner |
| 21738489 | Integrative analysis with global gene expression patterns in wild-type, Sirt6-/-, and double Sirt6-/- RelA-/- cells reveals the epistatic relationships between Sirt6 and RelA in shaping diverse temporal patterns of gene expression |
| 21738489 | Genes under the direct joint control of Sirt6 and RelA include several with prominent roles in cell senescence and organismal aging |
| 21738489 | These data suggest dynamic chromatin relocalization of Sirt6 as a key output of NF-kappaB signaling in stress response and aging |
| 21224216 | Accelerated epithelial cell senescence in IPF and the inhibitory role of SIRT6 in TGF-beta-induced senescence of human bronchial epithelial cells |
| 21224216 | Among the sirtuin (SIRT) family, SIRT6, a class III histone deacetylase, has been demonstrated to antagonize senescence |
| 21224216 | We evaluated the senescence of bronchiolization in association with SIRT6 expression in IPF lung |
| 21224216 | The changes of SIRT6, p21, and interleukin (IL)-1beta expression levels in HBEC, as well as type I collagen expression levels in fibroblasts, were evaluated |
| 21224216 | In IPF lung samples, an increase in markers of senescence and SIRT6 expression was found in the bronchial epithelial cells lining cystically remodeled air spaces |
| 21224216 | We found that TGF-beta induced senescence in primary HBEC by increasing p21 expression, and, whereas TGF-beta also induced SIRT6, it was not sufficient to inhibit cellular senescence |
| 21224216 | However, overexpression of SIRT6 efficiently inhibited TGF-beta-induced senescence via proteasomal degradation of p21 |
| 21224216 | These findings suggest that accelerated epithelial senescence plays a role in IPF pathogenesis through perpetuating abnormal epithelial-mesenchymal interactions, which can be antagonized by SIRT6 |
| 19135889 | SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span |
| 19135889 | Deficiency of mammalian SIRT6 leads to shortened life span and an aging-like phenotype in mice, but the underlying molecular mechanisms are unclear |
| 19135889 | Here we show that SIRT6 functions at chromatin to attenuate NF-kappaB signaling |
| 19135889 | SIRT6 interacts with the NF-kappaB RELA subunit and deacetylates histone H3 lysine 9 (H3K9) at NF-kappaB target gene promoters |
| 19135889 | We propose that SIRT6 attenuates NF-kappaB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-kappaB signaling may contribute to premature and normal aging |
| 18337721 | SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin |
| 18337721 | In mice, deficiency for the Sir2 family member SIRT6 leads to a shortened lifespan and a premature ageing-like phenotype |
| 18337721 | However, the molecular mechanisms of SIRT6 function are unclear |
| 18337721 | SIRT6 is a chromatin-associated protein, but no enzymatic activity of SIRT6 at chromatin has yet been detected, and the identity of physiological SIRT6 substrates is unknown |
| 18337721 | Here we show that the human SIRT6 protein is an NAD+-dependent, histone H3 lysine 9 (H3K9) deacetylase that modulates telomeric chromatin |
| 18337721 | SIRT6 associates specifically with telomeres, and SIRT6 depletion leads to telomere dysfunction with end-to-end chromosomal fusions and premature cellular senescence |
| 18337721 | At telomeric chromatin, SIRT6 deacetylates H3K9 and is required for the stable association of WRN, the factor that is mutated in Werner syndrome |
| 18337721 | We propose that SIRT6 contributes to the propagation of a specialized chromatin state at mammalian telomeres, which in turn is required for proper telomere metabolism and function |
| 18337721 | Our findings constitute the first identification of a physiological enzymatic activity of SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human premature ageing syndrome |
