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https://www.readbyqxmd.com/read/28435470/downregulation-of-sirt7-by-5-fluorouracil-induces-radiosensitivity-in-human-colorectal-cancer
#1
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
https://www.readbyqxmd.com/read/28426094/sirt7-dependent-deacetylation-of-cdk9-activates-rna-polymerase-ii-transcription
#2
Maximilian F Blank, Sifan Chen, Fabian Poetz, Martina Schnölzer, Renate Voit, Ingrid Grummt
SIRT7 is an NAD+-dependent protein deacetylase that regulates cell growth and proliferation. Previous studies have shown that SIRT7 is required for RNA polymerase I (Pol I) transcription and pre-rRNA processing. Here, we took a proteomic approach to identify novel molecular targets and characterize the role of SIRT7 in non-nucleolar processes. We show that SIRT7 interacts with numerous proteins involved in transcriptional regulation and RNA metabolism, the majority of interactions requiring ongoing transcription...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28406750/sirtuins-and-dna-damage-repair-sirt7-comes-to-play
#3
REVIEW
Berta N Vazquez, Joshua K Thackray, Lourdes Serrano
Aging is characterized by a cumulative loss of genome integrity, which involves chromatin reorganization, transcriptional dysregulation and the accumulation of DNA damage. Sirtuins participate in the protection against these aging processes by promoting genome homeostasis in response to cellular stress. We recently reported that SirT7(-/-) mice suffer from partial embryonic lethality and a progeroid like phenotype. At the cellular level, SIRT7 depletion results in the impaired repair of DNA double-strand breaks (DSBs), one the most dangerous DNA lesions, leading to genome instability...
March 4, 2017: Nucleus
https://www.readbyqxmd.com/read/28385812/sirtuin-7-is-decreased-in-pulmonary-fibrosis-and-regulates-the-fibrotic-phenotype-of-lung-fibroblasts
#4
Anne Elizabeth Wyman, Zahid Noor, Rita Fishelevich, Virginia Lockatell, Nirav G Shah, Nevins W Todd, Sergei P Atamas
Pulmonary fibrosis is a severe condition with no cure and limited therapeutic options. Better understanding of its pathophysiology is needed. Recent studies have suggested that pulmonary fibrosis may be driven by accelerated aging-related mechanisms. Sirtuins (SIRTs), particularly SIRT1, -3, and -6, are well-known mediators of aging, however limited data exist on the contribution of sirtuins to lung fibrosis. We assessed the mRNA and protein levels of all seven known sirtuins in primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) in comparison with lung fibroblasts from healthy controls...
April 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28242208/interplay-between-sirt1-and-hepatitis-b-virus-x-protein-in-the-activation-of-viral-transcription
#5
Jian-Jun Deng, Ka-Yiu Edwin Kong, Wei-Wei Gao, Hei-Man Vincent Tang, Vidyanath Chaudhary, Yun Cheng, Jie Zhou, Chi-Ping Chan, Danny Ka-Ho Wong, Man-Fung Yuen, Dong-Yan Jin
Hepatitis B virus (HBV) genome is organized into a minichromosome known as covalently closed circular DNA (cccDNA), which serves as the template for all viral transcripts. SIRT1 is an NAD(+)-dependent protein deacetylase which activates HBV transcription by promoting the activity of cellular transcription factors and coactivators. How SIRT1 and viral transactivator X protein (HBx) might affect each other remains to be clarified. In this study we show synergy and mutual dependence between SIRT1 and HBx in the activation of HBV transcription...
February 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28197299/sirtuins-expression-and-their-role-in-retinal-diseases
#6
REVIEW
Sankarathi Balaiya, Khaled K Abu-Amero, Altaf A Kondkar, Kakarla V Chalam
Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confer protection against oxidative stress and retinal degeneration. In mammals, the sirtuin (SIRT) family consists of seven proteins (SIRT1-SIRT7)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28177837/characteristics-of-expression-and-regulation-of-sirtuins-in-chicken-gallus-gallus
#7
Junxiao Ren, Naiyi Xu, Zheng Ma, Yanmin Li, Cuicui Li, Yanbin Wang, Yadong Tian, Xiaojun Liu, Xiangtao Kang
Sirtuins (SIRT1-SIRT7) are a family of NAD(+)-dependent protein deacetylases that are linked to post-translational regulation of many metabolic processes. There are few reports available for chicken sirtuins (designated cSIRT1-cSIRT7), whose expression and regulation in the liver have yet to be explored. In the present study, we characterized the expression and regulation of sirtuin family members in chicken liver. The results showed that the sirtuin family members in chicken share the same conserved functional SIR2 domains...
November 25, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28147277/regulation-of-serine-threonine-kinase-akt-activation-by-nad-dependent-deacetylase-sirt7
#8
Jia Yu, Bo Qin, Fengying Wu, Sisi Qin, Somaira Nowsheen, Shan Shan, Jacqueline Zayas, Huadong Pei, Zhenkun Lou, Liewei Wang
The Akt pathway is a central regulator that promotes cell survival in response to extracellular signals. Depletion of SIRT7, an NAD(+)-dependent deacetylase that is the least-studied sirtuin, is known to significantly increase Akt activity in mice through unknown mechanisms. In this study, we demonstrate that SIRT7 depletion in breast cancer cells results in Akt hyper-phosphorylation and increases cell survival following genotoxic stress. Mechanistically, SIRT7 specifically interacts with and deacetylates FKBP51 at residue lysines 28 and 155 (K28 and K155), resulting in enhanced interactions among FKBP51, Akt, and PHLPP, as well as Akt dephosphorylation...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28067587/the-seven-faces-of-sirt7
#9
Maximilian F Blank, Ingrid Grummt
SIRT7, a member of the sirtuin family of NAD(+)-dependent protein deacetylases, is a key mediator of many cellular activities. SIRT7 expression is linked to cell proliferation and oncogenic activity, connecting SIRT7-dependent regulation of ribosome biogenesis with checkpoints controlling cell cycle progression, metabolic homeostasis, stress resistance, aging and tumorigenesis. Despite this important functional link, the enzymatic activity, the molecular targets and physiological functions of SIRT7 are poorly defined...
March 15, 2017: Transcription
https://www.readbyqxmd.com/read/27997115/sirt7-is-an-rna-activated-protein-lysine-deacylase
#10
Zhen Tong, Miao Wang, Yi Wang, David D Kim, Jennifer K Grenier, Ji Cao, Sushabhan Sadhukhan, Quan Hao, Hening Lin
Mammalian SIRT7 is a member of the sirtuin family that regulates multiple biological processes including genome stability, metabolic pathways, stress responses, and tumorigenesis. SIRT7 has been shown to be important for ribosome biogenesis and transcriptional regulation. SIRT7 knockout mice exhibit complications associated with fatty liver and increased aging in hematopoietic stem cells. However, the molecular basis for its biological function remains unclear, in part due to the lack of efficient enzymatic activity in vitro...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/27923775/the-plasticizer-bbp-selectively-inhibits-epigenetic-regulator-sirtuin-during-differentiation-of-c3h10t1-2-stem-cell-line
#11
Jian Zhang, Mahua Choudhury
Exposure to environmental chemicals can perturb an individual's metabolic set point, especially during critical periods of development, and as a result increase his or her propensity towards obesity that is manifested later in life and possibly in successive generations. We hypothesized that benzyl butyl phthalate (BBP), a widespread endocrine disruptor, may impair one important epigenetic regulator, sirtuin, in mesenchymal stem cells and induce adipogenesis. Our results showed that gene expression of two well-known adipogenic markers, aP2 and PPARγ, were significantly increased from day 2 to day 8 under 50μM BBP exposure when compared to control in C3H10T1/2 stem cells (p<0...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27882448/sirtuins-and-their-roles-in-brain-aging-and-neurodegenerative-disorders
#12
Henryk Jęśko, Przemysław Wencel, Robert P Strosznajder, Joanna B Strosznajder
Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD(+) levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD(+)-dependent post-translational protein modifiers...
March 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27774669/acetylation-of-pgk1-promotes-liver-cancer-cell-proliferation-and-tumorigenesis
#13
Hongli Hu, Wenwei Zhu, Jun Qin, Min Chen, Liyan Gong, Long Li, Xiangyuan Liu, Yongzhen Tao, Huiyong Yin, Hu Zhou, Lisha Zhou, Dan Ye, Qinghai Ye, Daming Gao
Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism...
February 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27763519/segmental-aging-underlies-the-development-of-a-parkinson-phenotype-in-the-as-agu-rat
#14
Sohair M Khojah, Anthony P Payne, Dagmara McGuinness, Paul G Shiels
There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16(Ink4a), Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16(INK4a) expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions...
October 17, 2016: Cells
https://www.readbyqxmd.com/read/27761341/identification-and-temporal-expression-of-putative-circadian-clock-transcripts-in-the-amphipod-crustacean-talitrus-saltator
#15
Joseph F O'Grady, Laura S Hoelters, Martin T Swain, David C Wilcockson
BACKGROUND: Talitrus saltator is an amphipod crustacean that inhabits the supralittoral zone on sandy beaches in the Northeast Atlantic and Mediterranean. T. saltator exhibits endogenous locomotor activity rhythms and time-compensated sun and moon orientation, both of which necessitate at least one chronometric mechanism. Whilst their behaviour is well studied, currently there are no descriptions of the underlying molecular components of a biological clock in this animal, and very few in other crustacean species...
2016: PeerJ
https://www.readbyqxmd.com/read/27699588/the-protein-interaction-network-with-functional-roles-in-tumorigenesis-neurodegeneration-and-aging
#16
REVIEW
Jarmila Nahálková
The present review summarizes the knowledge about a protein-interaction network, which includes proteins with significant functions in the mechanisms of aging and age-related diseases. All the detected interacting proteins TPPII, p53, MYBBP1A, CDK2 and SIRT7, SIRT6, and CD147 are suitable for the development of antitumor therapeutics and treatments for diseases of aging. TPPII and SIRT6 directly affect glucose metabolism which drive malignant growth. In addition, SIRT6 activators are attractive candidates for Alzheimer's disease (AD) due to the protection effect of SIRT6 overexpression from DNA damage...
December 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27669435/the-interaction-between-acetylation-and-serine-574-phosphorylation-regulates-the-apoptotic-function-of-foxo3
#17
Z Li, B Bridges, J Olson, S A Weinman
The multispecific transcription factor and tumor suppressor FOXO3 is an important mediator of apoptosis, but the mechanisms that control its proapoptotic function are poorly understood. There has long been evidence that acetylation promotes FOXO3-driven apoptosis and recently a specific JNK (c-Jun N-terminal kinase)-dependent S574 phosphorylated form (p-FOXO3) has been shown to be specifically apoptotic. This study examined whether acetylation and S574 phosphorylation act independently or in concert to regulate the apoptotic function of FOXO3...
March 30, 2017: Oncogene
https://www.readbyqxmd.com/read/27628218/a-novel-role-for-sirt3-in-regulating-mediators-involved-in-the-terminal-pathways-of-human-labor-and-delivery
#18
Ratana Lim, Gillian Barker, Ramkumar Menon, Martha Lappas
Preterm birth remains the major cause of neonatal mortality and morbidity, mediated largely by an inflammatory process. The sirtuin (SIRT) family of cellular regulators has been implicated as key inhibitors of inflammation. We have previously reported a role for SIRT1, SIRT2, and SIRT6 in regulating inflammation-induced prolabor mediators. In this study, we determined the effect of term labor and pro-inflammatory cytokines on SIRT3, SIRT4, SIRT5, and SIRT7 expression in human myometrium. Functional studies were also used to investigate the effect of small interfering RNA (siRNA) knockdown of SIRTs in regulating inflammation-induced prolabor mediators...
November 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27599551/microrna-3666-induced-suppression-of-sirt7-inhibits-the-growth-of-non-small-cell-lung-cancer-cells
#19
Hongyang Shi, Yuqiang Ji, Dexin Zhang, Yun Liu, Ping Fang
Sirtuin7 (SIRT7) plays an important role in many cancer types, but its function in non-small cell lung cancer (NSCLC) remains unclear. This study investigated the biological role and underlying mechanism of SIRT7 in NSCLC. Results showed that SIRT7 was highly expressed in NSCLC cell lines, as detected by real-time quantitative polymerase chain reaction and western blot analysis. SIRT7 knockdown by small interfering RNA (siRNA) significantly inhibited the growth of NSCLC cells and induced their apoptosis. Bioinformatics algorithms indicated that SIRT7 was a putative target of microRNA-3666 (miR-3666)...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27592202/tissue-specific-regulation-of-sirtuin-and-nicotinamide-adenine-dinucleotide-biosynthetic-pathways-identified-in-c57bl-6-mice-in-response-to-high-fat-feeding
#20
Janice E Drew, Andrew J Farquharson, Graham W Horgan, Lynda M Williams
The sirtuin (SIRT)/nicotinamide adenine dinucleotide (NAD) system is implicated in development of type 2 diabetes (T2D) and diet-induced obesity, a major risk factor for T2D. Mechanistic links have not yet been defined. SIRT/NAD system gene expression and NAD/NADH levels were measured in liver, white adipose tissue (WAT) and skeletal muscle from mice fed either a low-fat diet or high-fat diet (HFD) for 3 days up to 16 weeks. An in-house custom-designed multiplex gene expression assay assessed all 7 mouse SIRTs (SIRT1-7) and 16 enzymes involved in conversion of tryptophan, niacin, nicotinamide riboside and metabolic precursors to NAD...
August 14, 2016: Journal of Nutritional Biochemistry
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