Ask about this productRelated genes to: SIRT6 antibody
- Gene:
- SIRT6 NIH gene
- Name:
- sirtuin 6
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2001-03-20
- Date modifiied:
- 2015-09-02
Related products to: SIRT6 antibody
Related articles to: SIRT6 antibody
- Sirtuins (SIRT1-SIRT7) are nicotinamide adenine dinucleotide (NAD) dependent deacylases that serves as metabolic sensors, coupling cellular energy status to chromatin structure, mitochondrial function, and stress responses. Dysregulated SIRT activity has been extensively studied in aging, metabolic syndrome, cardiovascular disease, neurodegeneration, cancer, and immune disorders. However, robust human evidence and SIRT-targeted therapies are lacking. Transgenic mouse models serve as key platforms to study gene function and guide therapeutic development. This review synthesizes evidence from transgenic mouse models regarding the core cellular processes governed by SIRTs: metabolism, genome integrity, stress resistance, immunity, and autophagy, and illustrates their operation across different organ systems. By comparing global, tissue-specific, and inducible knockout (KO) and overexpression (OE) models of cardiovascular, respiratory, digestive, nervous, endocrine, urogenital, musculoskeletal, malignant, and immune diseases, we identified central regulatory SIRTs (SIRT1, SIRT3, and SIRT6), context-dependent modifiers (SIRT2, SIRT4, SIRT5, and SIRT7), and their organ- and cell type-specific functions. We also summarize representative small-molecule SIRT activators, inhibitors, and degraders, covering both clinical and preclinical studies, and highlight where contradictions and knowledge gaps remain. Together, these analyses help clarify which aspects of SIRT modulation are most promising and under what isoform, tissue, and disease contexts they should be pursued for the development of SIRT‑targeted therapies in human disease. - Source: PubMed
Publication date: 2026/07/22
Wang Jia-YiJiang Feng-LiZhang Fang-YuanHuang Dong-HuiLi Xiao-YingGao SongYou HuaWu Qi-JunChen Huan-HuanGong Ting-Ting - The global incidence and prevalence of kidney diseases continue to rise, posing a serious public health challenge. SIRT6 is an NAD⁺-dependent histone deacetylase with broad essential regulatory roles across various pathophysiological processes, including DNA repair, chromatin accessibility, telomere stability, and glycolipid metabolism. As an epigenetic regulator specifically expressed in kidney tissues, SIRT6 serves as a central mediator of kidney homeostasis. Notably, accumulating evidence has implicated aberrant SIRT6 expression in the onset and development of various kidney diseases, such as acute kidney injury, diabetic kidney disease, hypertensive nephropathy, renal fibrosis, and renal cell carcinoma. In the present review, we provide an overview of the sirtuin family, systematically characterize the enzymatic activities and critical biological functions of SIRT6, and discuss its molecular mechanisms across various kidney diseases, focusing on its cell type-specific functions. We further summarize the latest research advances in SIRT6-targeted modulators for improving kidney diseases and analyze the challenges associated with their clinical application. Overall, we highlight SIRT6 as a highly promising novel target in the treatment and prevention of kidney diseases, with strong potential for clinical translation. - Source: PubMed
Publication date: 2026/07/17
Ren FeihongWang YudianZhang YufeiLiu LihengJin QiYang LipingZhan Yongli - Thyroid cancer (TC) is the most common endocrine malignancy, with incidence increasing worldwide. Although most differentiated TCs have a favorable prognosis, radioiodine (RAI)-refractory differentiated thyroid cancer (DTC), BRAF inhibitor-resistant papillary thyroid cancer, and anaplastic thyroid cancer (ATC) remain major areas of unmet clinical need. The sirtuin (SIRT) family of NAD-dependent enzymes has emerged as a multifaceted regulator of TC biology, with isoform-specific dichotomous roles: SIRT1, SIRT6, and SIRT7 act as tumor promoters through engagement of BRAF/MAPK, PI3K/AKT, epithelial-mesenchymal transition (EMT), and Hippo pathways, while SIRT3 and SIRT4 function as tumor suppressors via mitochondrial metabolic regulation. This review synthesizes recent developments that expand the therapeutic landscape: (i) the recognition that SIRT7 functions as a desuccinylase with preclinically identified oncogenic substrates, modifying KIF23 in ATC and LATS1 in PTC; (ii) the emerging roles of isoform-specific SIRT axes, including the NAMPT-SIRT1-PD-L1 axis, SIRT6-associated regulatory T-cell biology, and SIRT2 as a T-cell metabolic checkpoint, as determinants of immune microenvironment state and potential modulators of immune checkpoint inhibitor response; and (iii) the SIRT6-nuclear receptor coactivator 4 (NCOA4) ferritinophagy axis as a supported ferroptosis vulnerability in ATC, with potential but still hypothesis-generating relevance to dedifferentiated and RAI-refractory DTC. Importantly, the therapeutic logic for SIRT6 is disease-state-specific rather than contradictory: SIRT6 inhibition is rationalized in BRAF-driven aggressive PTC and DTC contexts where SIRT6 supports MAPK signaling, EMT, and ferroptosis resistance, whereas in SIRT6-high ATC, the same enzyme's NCOA4-dependent ferritinophagy activity may instead be exploited to enhance ferroptosis sensitivity. We review the current SIRT modulator pharmacological toolkit-including EX-527, OSS_128167, and emerging SIRT7-selective inhibitors-and identify the substantial clinical translation gap, with no SIRT-targeted clinical trial yet conducted in TC, despite strong preclinical rationale. We outline biomarker-stratified combination strategies with BRAF/MEK inhibitors, multikinase inhibitors, immune checkpoint inhibitors, and ferroptosis inducers, prioritizing biomarker-driven preclinical validation and, where supported by efficacy and safety data, subsequent early-phase evaluation in V600E-mutant and SIRT6-high thyroid cancer. Sirtuins thus represent a mechanistically promising and potentially biomarker-stratifiable therapeutic hypothesis for difficult-to-treat thyroid cancer; however, clinical translation remains at an early stage and requires validated biomarkers, isoform-selective compounds, and disease-specific in vivo evidence. - Source: PubMed
Publication date: 2026/06/27
Cho Ki JuSeo Ji HyunKwon HayeongLee Seung-JunHah Young-SoolPark Jung Je - Metabolic disorders such as obesity, type 2 diabetes mellitus, and fatty liver disease are associated with a disruption in the coordinated regulation of nutrient sensing, energy metabolism, and cellular homoeostasis. Increasing evidence indicates that sirtuins, a family of NAD-dependent enzymes, play a central role in integrating metabolic and stress-responsive pathways. By coupling the cellular redox state to transcriptional and post-translational regulation, sirtuins coordinate key processes such as glucose and lipid metabolism, mitochondrial function, and inflammatory signalling. Sirtuins are functionally specialised according to their subcellular localisation. Nuclear sirtuins (SIRT1, SIRT6, and SIRT7) regulate transcriptional programs controlling metabolism and inflammation, whereas mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5) directly modulate metabolic enzyme activity and redox homoeostasis. SIRT2 links cytosolic metabolic signalling to cytoskeletal dynamics and cell cycle regulation. Importantly, the activity of all sirtuins is tightly dependent on NAD availability, positioning NAD metabolism as a central regulator of the sirtuin network. In this review, we provide a systems-level perspective on sirtuin biology, highlighting how NAD metabolism, subcellular compartmentalisation, and specific functions converge to form an integrated regulatory network governing metabolic homoeostasis. We further discuss how disruption of this network contributes to the pathogenesis of metabolic disorders through impaired metabolic flexibility, mitochondrial dysfunction, and chronic inflammation. Overall, this network-based framework provides a unified view of sirtuin function in metabolic regulation and helps to explain the complexity and tissue-specific heterogeneity of metabolic diseases. - Source: PubMed
Szczęsny-Małysiak EwaSchiavoni ValentinaRotondo RossellaZeppa Sabrina DonatiVignini AriannaMoriconi EleonoraCecati MoniaArmani AndreaGorini StefaniaCampagna RobertoCaprio Massimiliano - Zearalenone (ZEA) is a prevalent mycotoxin in feed, known for its potent reproductive toxicity that poses a significant threat to male reproductive function. Sertoli cells (SCs) are essential for spermatogenesis. Although ZEA induces oxidative damage to SCs, the underlying mechanisms and effective prevention and control strategies remain underexplored. We found that ZEA treatment induced oxidative stress, increased γH2AX and tail moment, damaged cellular DNA, and consequently suppresses cell activity and function. Furthermore, exposure to ZEA diminishes the levels of DNA repair and antioxidant pathway proteins, thereby compromising both antioxidant capacity and DNA repair capabilities. PARP1 is the first key repair protein to identify DNA damage, and its catalytic poly(ADP-ribosyl)ation is a signal to recruit repair proteins. ZEA exposure increased PARP1, but reduced poly(ADP-ribosyl)ation and its downstream repair proteins, as well as antioxidant pathway proteins. This indicates that ZEA damages DNA and suppresses both DNA repair capacity and antioxidant defense capabilities. Inhibiting PARP1 further reduces DNA damage repair and antioxidant protein levels, thereby exacerbating DNA damage. NAD+ is the only substrate for PARP1 enzymatic reaction. NAD+ treatment increases the levels of DNA repair proteins and antioxidant proteins, and alleviates DNA damage caused by ZEA exposure. Furthermore, overexpression of sirt6 increased poly(ADP-ribosyl)ation and mitigated DNA damage, exerting a positive regulatory effect on alleviating ZEA toxicity. In summary, these findings underscore the regulatory function of PARP1 and its mediated poly(ADP-ribosyl)ation in ZEA-induced DNA damage in bovine SCs, offering new insights for mitigating ZEA-induced male reproductive dysfunction. - Source: PubMed
Publication date: 2026/07/13
Liu SongqiHe XinfengPang YunweiXu ShiyuanWu KaihuiHu JianhongWang Dong