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https://www.readbyqxmd.com/read/28923965/sirt7-promotes-adipogenesis-in-the-mouse-by-inhibiting-autocatalytic-activation-of-sirt1
#1
Jian Fang, Alessandro Ianni, Christian Smolka, Olesya Vakhrusheva, Hendrik Nolte, Marcus Krüger, Astrid Wietelmann, Nicolas G Simonet, Juan M Adrian-Segarra, Alejandro Vaquero, Thomas Braun, Eva Bober
Sirtuins (Sirt1-Sirt7) are NAD(+)-dependent protein deacetylases/ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28911000/dicer-regulates-non-homologous-end-joining-and-is-associated-with-chemosensitivity-in-colon-cancer-patients
#2
Xiao Chen, Wen-Feng Li, Xiaoli Wu, Heng-Chao Zhang, Li Chen, Pei-Ying Zhang, Li-Yuan Liu, Di Ma, Tongke Chen, Lingli Zhou, Yunsheng Xu, Meng-Tao Zhou, Kai-Fu Tang
DNA double-strand break (DSB) repair is an important mechanism underlying chemotherapy resistance in human cancers. Dicer participates in DSB repair by facilitating homologous recombination. However, whether Dicer is involved in non-homologous end joining (NHEJ) remains unknown. Here, we addressed whether Dicer regulates NHEJ and chemosensitivity in colon cancer cells. Using our recently developed NHEJ assay, we found that DSB introduction by I-SceI cleavage leads to Dicer upregulation. Dicer knockdown increased SIRT7 binding and decreased the level of H3K18Ac (acetylated lysine 18 of histone H3) at DSB sites, thereby repressing the recruitment of NHEJ factors to DSB sites and inhibiting NHEJ...
September 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28891317/the-role-of-sirtuins-in-antioxidant-and-redox-signaling
#3
Chandra K Singh, Gagan Chhabra, Mary Ndiaye, Liz Mariely Garcia-Peterson, Nicholas John Mack, Nihal Ahmad
SIGNIFICANCE: Antioxidant and redox signaling (ARS) events are regulated by critical molecules that modulate antioxidants, reactive oxygen or nitrogen species (ROS/RNS) and/or oxidative stress within the cell. Imbalances in these molecules can disturb cellular functions to become pathogenic. Sirtuins serve as important regulators of ARS in cells. Recent Advances: Sirtuins (SIRTs 1-7) are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases with the ability to deacetylate histone and non-histone targets...
September 11, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28886238/sirt7-deacetylates-ddb1-and-suppresses-the-activity-of-the-crl4-e3-ligase-complexes
#4
Yan Mo, Ran Lin, Peng Liu, Minjia Tan, Yue Xiong, Kun-Liang Guan, Hai-Xin Yuan
Cullin 4 (CUL4) and small ring finger protein ROC1 assemble to form E3 ubiquitin ligase (CRL4) complexes. CUL4 interacts with WD-40 proteins through the adaptor protein DDB1 to target substrates for ubiquitylation.. Very little is known on how the CUL4 and DDB1 interaction is regulated. Here, we show that DDB1 is acetylated and acetylation promotes DDB1 binding to CUL4. We also identify nucleolar SIRT7 as a major deacetylase that negatively regulates DDB1-CUL4 interaction. Following inhibition of nucleolar function by Actinomycin D (ActD) or 5-Fluorouracil (5-FU) treatment or knocking down Pol I component UBF, SIRT7 is mobilized from the nucleolus to the nucleoplasm and promotes DDB1 deacetylation, leading to decreased DDB1-CUL4 association and CRL4 activity...
September 8, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28880264/knockdown-of-sirt7-enhances-the-osteogenic-differentiation-of-human-bone-marrow-mesenchymal-stem-cells-partly-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#5
Erman E M Chen, Wei Zhang, Chenyi C Y Ye, Xiang Gao, Liangjun L J Jiang, Tengfei T F Zhao, Zhijun Z J Pan, Deting D T Xue
Sirtuin 7 (SIRT7) is a NAD(+)-dependent deacetylase in the sirtuin family. In a previous study, human bone marrow mesenchymal stem cells (hBMSCs) with reduced SIRT7 activity were developed to evaluate the effect of SIRT7 on osteogenesis. SIRT7 knockdown significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Additionally, SIRT7 knockdown upregulated β-catenin. The enhanced osteogenesis due to SIRT7 knockdown was partially rescued by a Wnt/β-catenin inhibitor...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28842251/sirt7-stabilizes-rdna-heterochromatin-through-recruitment-of-dnmt1-and-sirt1
#6
Alessandro Ianni, Soraya Hoelper, Marcus Krueger, Thomas Braun, Eva Bober
Maintenance of highly compact heterochromatin at ribosomal DNA (rDNA) segments is essential to prevent homologous recombination between rDNA repeats and for preserving genomic stability and nucleolar architecture. Here, we investigated the role of Sirtuin 7 (Sirt7) in the regulation of rDNA chromatin structure, rDNA repeat stability and nucleolar organization. We found that Sirt7 mediates heterochromatin formation at rRNA genes through recruitment of DNA methyltransferase 1 and another member of the sirtuin family, Sirt1...
August 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28827661/sirt7-antagonizes-tgf-%C3%AE-signaling-and-inhibits-breast-cancer-metastasis
#7
Xiaolong Tang, Lei Shi, Ni Xie, Zuojun Liu, Minxian Qian, Fanbiao Meng, Qingyang Xu, Mingyan Zhou, Xinyue Cao, Wei-Guo Zhu, Baohua Liu
Distant metastasis is the main cause of breast cancer-related death; however, effective therapeutic strategies targeting metastasis are still scarce. This is largely attributable to the spatiotemporal intratumor heterogeneity during metastasis. Here we show that protein deacetylase SIRT7 is significantly downregulated in breast cancer lung metastases in human and mice, and predicts metastasis-free survival. SIRT7 deficiency promotes breast cancer cell metastasis, while temporal expression of Sirt7 inhibits metastasis in polyomavirus middle T antigen breast cancer model...
August 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28790157/sirt7-and-the-dead-box-helicase-ddx21-cooperate-to-resolve-genomic-r-loops-and-safeguard-genome-stability
#8
Chenlin Song, Agnes Hotz-Wagenblatt, Renate Voit, Ingrid Grummt
R loops are three-stranded nucleic acid structures consisting of an RNA:DNA heteroduplex and a "looped-out" nontemplate strand. As aberrant formation and persistence of R loops block transcription elongation and cause DNA damage, mechanisms that resolve R loops are essential for genome stability. Here we show that the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase DDX21 efficiently unwinds R loops and that depletion of DDX21 leads to accumulation of cellular R loops and DNA damage. Significantly, the activity of DDX21 is regulated by acetylation...
August 8, 2017: Genes & Development
https://www.readbyqxmd.com/read/28772218/suppression-of-microrna-142-5p-attenuates-hypoxia-induced-apoptosis-through-targeting-sirt7
#9
Liying Zhan, Shaoqing Lei, Wenlan Li, Yuan Zhang, Huaxin Wang, Yan Shi, Yulong Tian
Increasing study has suggested that microRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced injury. miR-142-5p has been suggested as a critical regulator for cellular survival. However, the role of miR-142-5p in regulating hypoxia-induced injury remains unknown. In this study, we aimed to investigate the mechanistic roles of miR-142-5p in regulating cell survival during hypoxia treatment using H9C2 cardiomyoblasts and primary cardiomyocytes. We showed that miR-142-5p expression level was significantly repressed by hypoxia treatment...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28768896/the-effects-of-graded-levels-of-calorie-restriction-xi-evaluation-of-the-main-hypotheses-underpinning-the-life-extension-effects-of-cr-using-the-hepatic-transcriptome
#10
Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan...
July 31, 2017: Aging
https://www.readbyqxmd.com/read/28675767/sirtuin7-is-involved-in-protecting-neurons-against-oxygen-glucose-deprivation-and-reoxygenation-induced-injury-through-regulation-of-the-p53-signaling-pathway
#11
Jianrui Lv, Junbin Tian, Guoxi Zheng, Jing Zhao
Sirtuin7 (SIRT7) is known to regulate apoptosis and stress responses. So far, very little is known about the role of SIRT7 in cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the potential role of SIRT7 in regulating oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in neurons. We found a significant increase of SIRT7 expression in neurons in response to OGD/R treatment. Knockdown of SIRT7 aggravated OGD/R-induced injury. Knockdown of SIRT7 augmented the levels of total and acetylated p53 protein...
July 4, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28661724/sirt1-and-sirt6-signaling-pathways-in-cardiovascular-disease-protection
#12
Nunzia D'Onofrio, Luigi Servillo, Maria Luisa Balestrieri
SIGNIFICANCE: Oxidative stress represents the common hallmark of pathological conditions associated with cardiovascular disease (CVD), including atherosclerosis, heart failure, hypertension, aging, diabetes, and other vascular system-related diseases. The sirtuin (SIRT) family, comprising seven proteins (SIRT1-SIRT7) sharing a highly conserved nicotinamide adenine dinucleotide (NAD(+))-binding catalytic domain, attracted a great attention for the past few years as stress adaptor and epigenetic enzymes involved in the cellular events controlling aging-related disorder, cancer, and CVD...
June 29, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28655758/ubiquitin-specific-peptidase-7-usp7-mediated-deubiquitination-of-the-histone-deacetylase-sirt7-regulates-gluconeogenesis
#13
Lu Jiang, Jiannan Xiong, Junsi Zhan, Fengjie Yuan, Ming Tang, Chaohua Zhang, Ziyang Cao, Yongcan Chen, Xiaopeng Lu, Yinglu Li, Hui Wang, Lina Wang, Jiadong Wang, Wei-Guo Zhu, Haiying Wang
Sirtuin 7 (SIRT7), a member of the NAD(+)-dependent class III histone deacetylases, is involved in the regulation of various cellular processes and in resisting various stresses, such as hypoxia, low glucose levels, and DNA damage. Interestingly, SIRT7 is linked to the control of glycolysis, suggesting a role in glucose metabolism. Given the important roles of SIRT7, it is critical to clarify how SIRT7 activity is potentially regulated. It has been reported that some transcriptional and post-transcriptional regulatory mechanisms are involved...
August 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28623141/sirtuin-7-dependent-deacetylation-of-ddb1-regulates-the-expression-of-nuclear-receptor-tr4
#14
Md Fazlul Karim, Tatsuya Yoshizawa, Shihab U Sobuz, Yoshifumi Sato, Kazuya Yamagata
Sirtuin 7 (SIRT7) is an NAD(+)-dependent deacetylase/deacylase, but only a limited number of SIRT7 substrates have been identified. Recently, we found that Sirt7 knockout mice are resistant to high-fat diet-induced fatty liver, and that SIRT7 positively regulates the protein level of TR4, a nuclear receptor involved in lipid metabolism, by inhibiting the CUL4B/DDB1/DCAF1 E3 ubiquitin ligase complex. However, the mechanism by which SIRT7 inhibits the E3 ubiquitin ligase complex was not identified. Here, we demonstrate that SIRT7 binds directly to DDB1 and deacetylates DDB1 at Lys1121...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28613014/raising-the-list-of-sirt7-targets-to-a-new-level
#15
Nicolas G Simonet, Alejandro Vaquero
Sirtuins are crucial proteins involved in sensing and coordinating the response to different forms of stress, mainly through NAD(+) -dependent deacetylation of proteins. For that reason, sirtuins are directly involved in many human pathologies including cancer, diabetes, cardiovascular and neurodegenerative diseases. SirT7, one of the less well-understood sirtuins, has been associated with ribosome biogenesis, gene expression, metabolism and cancer. Despite the wide range of these functions, only a handful of targets for SirT7 have so far been described...
June 14, 2017: Proteomics
https://www.readbyqxmd.com/read/28582407/enhanced-expression-and-phosphorylation-of-sirt7-activates-smad2-and-erk-signaling-and-promotes-the-cardiac-fibrosis-differentiation-upon-angiotensin-ii-stimulation
#16
Haichen Wang, Shengwu Liu, Shengqiang Liu, Wei Wei, Xiaolong Zhou, Fang Lin, Juanjuan Wang, Jinye Chen, Guodong Zhang, Yongbing Pang
Cardiac fibroblasts (CFs) phenotypic conversion to myofibroblasts (MFs) represents a crucial event in cardiac fibrosis that leads to impaired cardiac function. However, regulation of this phenotypic transformation remains unclear. Here, we showed that sirtuin-7 (Sirt7) plays an important role in the regulation of MFs differentiation. Sirt7 expression and phosphorylation were upregulated in CFs upon angiotensin-II (Ang-II) stimulation. Sirt7 depletion by siRNA in CFs resulted in decreased cell proliferation and extracellular matrix (ECM) deposition...
2017: PloS One
https://www.readbyqxmd.com/read/28562315/aged-induced-pluripotent-stem-cell-ipscs-as-a-new-cellular-model-for-studying-premature-aging
#17
Stefania Petrini, Rossella Borghi, Valentina D'Oria, Fabrizia Restaldi, Sandra Moreno, Antonio Novelli, Enrico Bertini, Claudia Compagnucci
Nuclear integrity and mechanical stability of the nuclear envelope (NE) are conferred by the nuclear lamina, a meshwork of intermediate filaments composed of A- and B-type lamins, supporting the inner nuclear membrane and playing a pivotal role in chromatin organization and epigenetic regulation. During cell senescence, nuclear alterations also involving NE architecture are widely described. In the present study, we utilized induced pluripotent stem cells (iPSCs) upon prolonged in vitro culture as a model to study aging and investigated the organization and expression pattern of NE major constituents...
May 31, 2017: Aging
https://www.readbyqxmd.com/read/28560068/hdac2-overexpression-correlates-with-aggressive-clinicopathological-features-and-dna-damage-response-pathway-of-breast-cancer
#18
Wenqi Shan, Yuanyuan Jiang, Huimei Yu, Qianhui Huang, Lanxin Liu, Xuhui Guo, Lei Li, Qingsheng Mi, Kezhong Zhang, Zengquan Yang
There are 18 lysine deacetylases, also known as histone deacetylases (HDACs), that remove acetyl groups from histone and non-histone proteins, thereby playing critical roles in numerous biological processes. In many human cancers, HDACs are dysregulated through mutation, altered expression, or inappropriate recruitment to certain loci. However, knowledge of the genomic and transcriptomic alterations and the clinical significance of most HDACs in breast cancer remain incomplete. We used TCGA and METABRIC datasets to perform comprehensive, integrated genomic and transcriptomic analyses of 18 HDAC genes in approximately 3000 primary breast cancers and identified associations among recurrent copy number alteration, gene expression, clinicopathological features, and patient survival...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28556401/quantitative-proteome-based-systematic-identification-of-sirt7-substrates
#19
Chaohua Zhang, Zichao Zhai, Ming Tang, Zhongyi Cheng, Tingting Li, Haiying Wang, Wei-Guo Zhu
SIRT7 is a class III histone deacetylase that is involved in numerous cellular processes. Only six substrates of SIRT7 have been reported thus far, so we aimed to systematically identify SIRT7 substrates using stable-isotope labeling with amino acids in cell culture (SILAC) coupled with quantitative mass spectrometry (MS). Using SIRT7(+/+) and SIRT7(-/-) mouse embryonic fibroblasts as our model system, we identified and quantified 1,493 acetylation sites in 789 proteins, of which 261 acetylation sites in 176 proteins showed ≥2-fold change in acetylation state between SIRT7(-/-) and SIRT7(+/+) cells...
May 27, 2017: Proteomics
https://www.readbyqxmd.com/read/28435470/downregulation-of-sirt7-by-5-fluorouracil-induces-radiosensitivity-in-human-colorectal-cancer
#20
Ming Tang, Xiaopeng Lu, Chaohua Zhang, Changzheng Du, Linlin Cao, Tianyun Hou, Zhiming Li, Bo Tu, Ziyang Cao, Yinglu Li, Yongcan Chen, Lu Jiang, Hui Wang, Lina Wang, Baohua Liu, Xingzhi Xu, Jianyuan Luo, Jiadong Wang, Jin Gu, Haiying Wang, Wei-Guo Zhu
5-Fluorouracil (5-FU) combined with radiotherapy is a common treatment strategy to treat human cancers, but the underlying mechanisms of this combination treatment remain unclear. Here, we report that NAD(+)-dependent deacetylase sirtuin-7 (SIRT7) protein levels were decreased due to 5-FU exposure rendering colorectal cancer cells sensitive to radiation. We found that SIRT7 downregulation was mediated via a Tat-binding Protein 1 (TBP1) proteasome-dependent pathway. Specifically, TBP1 was dephosphorylated at tyrosine 381 upon 5-FU treatment, which enhanced its direct interaction with SIRT7 and targeted it for degradation...
2017: Theranostics
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