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WT/SIRT6 KO 293T cell AP-MS anti-CDH1-HA

ABSTRACT: The study found reciprocal regulation between SIRT6 and APC/C. While SIRT6 is ubiquitinated by APC/C and degraded, CDH1, a co-activator of APC/C, is also deacetylated by SIRT6 and degraded.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Helin Wang

LAB HEAD: Haiteng Deng

PROVIDER: PXD022402 | Pride | 2021-09-09

REPOSITORIES: Pride

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Reciprocal interaction between SIRT6 and APC/C regulates genomic stability.

Wang Helin H Feng Kangze K Wang Qingtao Q Deng Haiteng H

Scientific reports 20210709 1

SIRT6 is an NAD<sup>+</sup>-dependent deacetylase that plays an important role in mitosis fidelity and genome stability. In the present study, we found that SIRT6 overexpression leads to mitosis defects and aneuploidy. We identified SIRT6 as a novel substrate of anaphase-promoting complex/cyclosome (APC/C), which is a master regulator of mitosis. Both CDH1 and CDC20, co-activators of APC/C, mediated SIRT6 degradation via the ubiquitination-proteasome pathway. Reciprocally, SIRT6 also deacetylate ...[more]

PMID: 34244565

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293T cell mitotic AP-MS anti-SIRT6-FLAG 201113

Project description:The study found reciprocal regulation between SIRT6 and APC/C. While SIRT6 is ubiquitinated by APC/C and degraded, CDH1, a co-activator of APC/C, is also deacetylated by SIRT6 and degraded.

2021-09-09 | PXD022500 | Pride

SIRT6 suppresses pancreatic cancer through control of Lin28b [ChIP-seq]

Project description:Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1 and IGF2BP3. This epigenetic program defines a distinct subset representing 30-40% of human PDAC, characterized by poor prognosis and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor, and uncover the Lin28b pathway as a potential therapeutic target in a molecularlydefined PDAC subset. ChIP-Seq experiments to examine H3K56ac histone modifications in murine PDAC cells that are Sirt6 wild type (WT), Sirt6 knock-out (KO), and Sirt6 KO cells engineered to express Sirt6 WT (Sirt6 KO + Sirt6 WT Restored).

2016-04-01 | E-GEOD-79503 | biostudies-arrayexpress

SIRT6 and SIRT7 binding proteome

Project description:To find the SIRT6 and SIRT7 binding proteins, we expressed V5-tagged SIRT6 and SIRT7 and pulled down this protein with anti-V5 agarose affinity gel. Sirtuins are a family of NAD-dependent deacetylases which deacetylate not only histones but also a wide range of target proteins. Sirtuins are conserved from yeast to mammal, and are known to regulate many processes such as cellular metabolism, apoptosis, cellular senescence, cell cycle, and organism-level aging. Among the members of sirtuins showing different subcellular localization, SIRT1, SIRT6 and SIRT7 are localized in nucleus. Whereas many functions and interacting proteins of SIRT1 have been studied, functions of SIRT6 and SIRT7 are not extensively revealed yet. Since it is important to understand the molecular function of SIRT6 and SIRT7, we here aimed to identify interacting proteins in mammalian cells.<br>Extra primary submitter: <a href="mailto:nglee@postech.ac.kr" target="_top">Namgyu Lee</a>, Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Republic of Korea<br>Lab head: <a href="mailto:kchoi@postech.ac.kr" target="_top">Kwan Yong Choi</a>, Department of Life Sciences and Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, 790-784, Republ ic of Korea

2014-04-28 | PXD000159 | Pride

SIRT6 regulates redox homeostasis in human mesenchymal stem cells by the transactivation of NRF2

Project description:We investigated the effect of SIRT6-knockout on gene expression and H3K4me3 modification profile in human mesenchymal stem cells. RNAs isolated from SIRT6+/+ and SIRT6-/- hMSCs at early and late passages were sequenced, respectively. And, H3K4me3 ChIP-seq was performed upon the SIRT6 deleted hMSC and WT at early stage, respectively.

2016-01-04 | E-GEOD-64642 | biostudies-arrayexpress

Sirt6 in Hepatocytes

Project description:The aim of our study was to identify differentially regulated genes specifically in hepatocytes (versus in total liver extracts) when Sirt6 is deleted.

2015-01-10 | E-MTAB-1477 | biostudies-arrayexpress

Sirt6 transgene mice

Project description:The significant increase in the human life-span during the last century confronts us with great medical challenges. To answer them, one must understand and control the mechanisms that determine healthy ageing. The highly conserved sirtuin deacetylases were shown to regulate life-span in lower organisms. Yet, the role of mammalian sirtuins, SIRT1 to 7, in regulating life-span is currently unclear. Here, we show that in SIRT6 transgenic mice (Sirt6-tg), the males but not the females, have a significant increase in life-span. Gene expression analysis revealed significant differences for male Sirt6-tg in comparison to male wild-type mice. Transgenic males display lower serum IGF-1 levels, increased levels of IGFBP-1 and altered phosphorylation levels of major components of the IGF-1 pathway, a key factor in the regulation of life-span. This study is the first to show regulation of mammalian life-span by a sirtuin family member, and has important therapeutic implications for age-related diseases.

2012-04-01 | E-MTAB-871 | biostudies-arrayexpress

Cdh1 (Fzr1) Interactome in Neuroblastoma (N2A) cells

Project description:In this study, we wanted to explore the protein interactors of Cdh1, a subunit of the E3 Ubiquitin-Ligase Cdh1-APC. Our data show that in addition to interacting with other components of the Cdh1-APC complex, Cdh1 interacts with regulators of translation.

2020-04-29 | PXD018875 | Pride

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A

Project description:Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in the regulation of aging and metabolism. Targeted sequencing identified a SIRT6 allele containing two linked substitutions (N308K/A313S) as enriched in Ashkenazi Jewish (AJ) centenarians as compared to AJ control individuals. Characterization of this SIRT6 (centSIRT6) allele demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double strand break repair, and more robust cancer cell killing compared to the wild type. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

2022-10-21 | PXD035689 | Pride

SIRT6 and SIRT1 contribute to circadian gene expression

Project description:Comparison of the hepatic circadian transcriptomes reveals that SIRT6 and SIRT1 separately control transcriptional specificity, and therefore, define distinctly partitioned classes of circadian genes. Livers from WT and SIRT6 KO mice, and livers from WT and SIRT1 KO mice, were harvested over the circadian cycle at ZT 0, 4, 8, 12, 16 and 20 for gene expression analysis.

2014-08-05 | E-GEOD-57830 | biostudies-arrayexpress

SIRT6 regulates glucose metabolism and glutamatergic synapse in the mouse retina

Project description:Microarray analysis on total retinal RNA from 15 day old Sirt6 wild-type (WT) and knock-out (KO) mice. The retina is one of the major energy consuming tissues within the body. In this context, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is a highly demanding energy consuming process. Sirtuin 6 (SIRT6), a NAD-dependent deacylase, plays a key role in regulating glucose metabolism. In this study, we demonstrate that SIRT6 is highly expressed in the retina, controlling levels of histone H3K9 and H3K56 acetylation. Notably, despite apparent normal histology, SIRT6 deficiency caused major retinal transmission defects concomitant to changes in expression of glycolytic genes and glutamate receptors, as well as elevated levels of apoptosis in inner retina cells. Our results identify SIRT6 as a critical modulator of retinal function, likely through its effects on chromatin. Microarray analysis of total retinal RNA from 15 day old Sirt6 wild-type (WT) and knock-out (KO) mice with 3 replicates in each condition using the Affymetrix Mouse Gene 2.1 ST array (transcript (gene) version).

2014-07-30 | E-GEOD-56563 | biostudies-arrayexpress

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