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https://www.readbyqxmd.com/read/28501776/inhibition-of-senp3-by-urb597-ameliorates-neurovascular-unit-dysfunction-in-rats-with-chronic-cerebral-hypoperfusion
#1
Da-Peng Wang, Ke-Jia Liu, Graham Kasper, Qi Lin, Jian Hai
Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28446721/senp3-grants-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#2
Di Wu, Chun-Jie Huang, Faheem Ahmed Khan, Xiao-Fei Jiao, Xiao-Ming Liu, Nuruliarizki Shinta Pandupuspitasari, Rahim Dad Brohi, Li-Jun Huo
Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28351334/upregulation-of-senp3-smt3ip1-promotes-epithelial-ovarian-cancer-progression-and-forecasts-poor-prognosis
#3
Jialin Cheng, Min Su, Yunfeng Jin, Qinghua Xi, Yan Deng, Jie Chen, Wei Wang, Yannan Chen, Lingling Chen, Nannan Shi, Guoxin Mao
As a crucial member of the small ubiquitin-like modifier system, SUMO-specific protease 3, was identified to be essential for cell proliferation and ribosomal RNA processing. Recent studies showed that SUMO-specific protease 3 was elevated in ovarian cancer compared to normal tissue samples. However, the connection between SUMO-specific protease 3-specific expression and clinicopathological parameters of epithelial ovarian cancer, as well as the physiologically potential role of SUMO-specific protease 3 in epithelial ovarian cancer remained unclear...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344658/flightless-i-governs-cell-fate-by-recruiting-the-sumo-isopeptidase-senp3-to-distinct-hox-genes
#4
Arnab Nayak, Anja Reck, Christian Morsczeck, Stefan Müller
BACKGROUND: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood. RESULTS: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28321049/protective-effect-of-senp3-mediated-sumoylation-against-cadmium-toxicity
#5
Hongquan Zhu
SUMOylation is widely reported as a cytoprotective response against cell stress induced by ischemia and reperfusion. However, it is still unclear what other cell stressors trigger protein SUMOylation, what mechanisms enhance and maintain the enhanced SUMOylation, and if it is a general protective mediator against other cytotoxic stresses, toxic heavy metal cadmium for instance. Here, we show increased levels of SUMOylation and decreased levels of the deSUMOylation enzyme SENP3 in PC12 cells exposed to CdCl2...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28296937/effects-of-circadian-clock-genes-and-health-related-behavior-on-metabolic-syndrome-in-a-taiwanese-population-evidence-from-association-and-interaction-analysis
#6
Eugene Lin, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Shih-Jen Tsai
Increased risk of developing metabolic syndrome (MetS) has been associated with the circadian clock genes. In this study, we assessed whether 29 circadian clock-related genes (including ADCYAP1, ARNTL, ARNTL2, BHLHE40, CLOCK, CRY1, CRY2, CSNK1D, CSNK1E, GSK3B, HCRTR2, KLF10, NFIL3, NPAS2, NR1D1, NR1D2, PER1, PER2, PER3, REV1, RORA, RORB, RORC, SENP3, SERPINE1, TIMELESS, TIPIN, VIP, and VIPR2) are associated with MetS and its individual components independently and/or through complex interactions in a Taiwanese population...
2017: PloS One
https://www.readbyqxmd.com/read/28262828/senp3-mediated-desumoylation-of-drp1-facilitates-interaction-with-mff-to-promote-cell-death
#7
Chun Guo, Kevin A Wilkinson, Ashley J Evans, Philip P Rubin, Jeremy M Henley
The GTPase dynamin-related protein 1 (Drp1) is essential for physiological and pathophysiological mitochondrial fission. DeSUMOylation of Drp1 by the enzyme SENP3 promotes cell death during reperfusion after ischaemia by enhancing Drp1 partitioning to the mitochondrial outer membrane (MOM), which causes cytochrome c release and apoptosis. However, how deSUMOylation recruits Drp1 to the MOM is unknown. Here we show that deSUMOylation selectively promotes Drp1 binding to the MOM resident adaptor protein mitochondrial fission factor (Mff)...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27853276/sumo-specific-protease-3-is-a-key-regulator-for-hepatic-lipid-metabolism-in-non-alcoholic-fatty-liver-disease
#8
Yuhan Liu, Fudong Yu, Yan Han, Qing Li, Zhujun Cao, Xiaogang Xiang, Shaowen Jiang, Xiaolin Wang, Jie Lu, Rongtao Lai, Hui Wang, Wei Cai, Shisan Bao, Qing Xie
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in hepatocytes. The role of SENP3 in lipid metabolism, particularly NAFLD, is unclear. Our results showed that hepatic SENP3 was up-regulated in NAFLD patients and an animal model in vivo and after loading hepatocytes with free fatty acids (FFA) in vitro. Intracellular lipid accumulation was determined in SENP3 silenced or overexpressed hepatocytes with/without FFA in vitro. Confirming a role for SENP3, gene silencing was associated in vitro with amelioration of lipid accumulation and overexpression with enhancement of lipid accumulation...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27814492/the-aaa-atpase-mdn1-acts-as-a-sumo-targeted-regulator-in-mammalian-pre-ribosome-remodeling
#9
Nithya Raman, Elisabeth Weir, Stefan Müller
Biogenesis of translation-competent 80S ribosomes is a multi-step process requiring the sequential action of non-ribosomal trans-acting factors. We previously identified the human PELP1-TEX10-WDR18 complex and the associated SUMO isopeptidase SENP3 as regulators of 60S maturation. We provided evidence that deconjugating SUMO from PELP1 by SENP3 is instrumental for proper ribosome biogenesis. Here we show that SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27682256/impact-of-heat-stress-on-cellular-and-transcriptional-adaptation-of-mammary-epithelial-cells-in-riverine-buffalo-bubalus-bubalis
#10
Neha Kapila, Ankita Sharma, Amit Kishore, Monika Sodhi, Pawan K Tripathi, Ashok K Mohanty, Manishi Mukesh
The present study aims to identify the heat responsive genes and biological pathways in heat stressed buffalo mammary epithelial cells (MECs). The primary mammary epithelial cells of riverine buffalo were exposed to thermal stress at 42°C for one hour. The cells were subsequently allowed to recover at 37°C and harvested at different time intervals (30 min to 48 h) along with control samples (un-stressed). In order to assess the impact of heat stress in buffalo MECs, several in-vitro cellular parameters (lactate dehydrogenase activity, cell proliferation assay, cellular viability, cell death and apoptosis) and transcriptional studies were conducted...
2016: PloS One
https://www.readbyqxmd.com/read/27626674/sumo-signaling-by-hypoxic-inactivation-of-sumo-specific-isopeptidases
#11
Kathrin Kunz, Kristina Wagner, Luca Mendler, Soraya Hölper, Nathalie Dehne, Stefan Müller
Post-translational modification of proteins with ubiquitin-like SUMO modifiers is a tightly regulated and highly dynamic process. The SENP family of SUMO-specific isopeptidases comprises six cysteine proteases. They are instrumental in counterbalancing SUMO conjugation, but their regulation is not well understood. We demonstrate that in hypoxic cell extracts, the catalytic activity of SENP family members, in particular SENP1 and SENP3, is inhibited in a rapid and fully reversible process. Comparative mass spectrometry from normoxic and hypoxic cells defines a subset of hypoxia-induced SUMO1 targets, including SUMO ligases RanBP2 and PIAS2, glucose transporter 1, and transcriptional regulators...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27604867/sumoylation-regulates-the-intracellular-fate-of-zo-2
#12
Franziska Wetzel, Sonnhild Mittag, Misael Cano-Cortina, Tobias Wagner, Oliver H Krämer, Rainer Niedenthal, Lorenza Gonzalez-Mariscal, Otmar Huber
The zonula occludens (ZO)-2 protein links tight junctional transmembrane proteins to the actin cytoskeleton and associates with splicing and transcription factors in the nucleus. Multiple posttranslational modifications control the intracellular distribution of ZO-2. Here, we report that ZO-2 is a target of the SUMOylation machinery and provide evidence on how this modification may affect its cellular distribution and function. We show that ZO-2 associates with the E2 SUMO-conjugating enzyme Ubc9 and with SUMO-deconjugating proteases SENP1 and SENP3...
January 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27181202/sumoylation-and-senp3-regulate-stat3-activation-in-head-and-neck-cancer
#13
Z Zhou, M Wang, J Li, M Xiao, Y E Chin, J Cheng, E T H Yeh, J Yang, J Yi
Hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) has been found in various types of human cancers, including head and neck cancer (HNC). Although smoking is critical in the development and progression of HNC, how tobacco components activate STAT3 is unclear. We demonstrated that exposure of HNC cell lines to a tobacco extract induced a rapid Y705 phosphorylation of STAT3 and a rapid increase in the SUMO protease SENP3 that depended on a simultaneous increase in reactive oxygen species...
November 10, 2016: Oncogene
https://www.readbyqxmd.com/read/27016777/dynamic-regulation-of-hif1%C3%AE-stability-by-sumo2-3-and-senp3-in-the-human-placenta
#14
Jayonta Bhattacharjee, Sruthi Alahari, Julien Sallais, Andrea Tagliaferro, Martin Post, Isabella Caniggia
INTRODUCTION: Hypoxia-inducible factor 1A (HIF1A) stability is tightly regulated by hydroxylation and ubiquitination. Emerging evidence indicates that HIF1A is also controlled by the interplay between SUMO-specific ligases, which execute protein SUMOylation, and Sentrin/SUMO-specific proteases that de-SUMOylate target proteins. Given the significance of HIF1A in the human placenta, we investigated whether placental HIF1A is subject to SUMOylation in physiological and pathological conditions...
April 2016: Placenta
https://www.readbyqxmd.com/read/26522917/evaluation-of-the-activity-and-substrate-specificity-of-the-human-senp-family-of-sumo-proteases
#15
Andreia V Mendes, Cláudia P Grou, Jorge E Azevedo, Manuel P Pinto
Protein modification with the small ubiquitin-like modifier (SUMO) is a reversible process regulating many central biological pathways. The reversibility of SUMOylation is ensured by SUMO proteases many of which belong to the sentrin/SUMO-specific protease (SENP) family. In recent years, many advances have been made in allocating SENPs to specific biological pathways. However, due to difficulties in obtaining recombinant full-length active SENPs for thorough enzymatic characterization, our knowledge on these proteases is still limited...
January 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26511642/senp3-regulates-the-global-protein-turnover-and-the-sp1-level-via-antagonizing-sumo2-3-targeted-ubiquitination-and-degradation
#16
Ming Wang, Jing Sang, Yanhua Ren, Kejia Liu, Xinyi Liu, Jian Zhang, Haolu Wang, Jian Wang, Amir Orian, Jie Yang, Jing Yi
SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1...
January 2016: Protein & Cell
https://www.readbyqxmd.com/read/26493771/the-sumo-protease-senp3-orchestrates-g2-m-transition-and-spindle-assembly-in-mouse-oocytes
#17
Chun-Jie Huang, Di Wu, Faheem Ahmed Khan, Li-Jun Huo
Oocyte meiosis is a transcription quiescence process and the cell-cycle progression is coordinated by multiple post-translational modifications, including SUMOylation. SENP3 an important deSUMOylation protease has been intensively studied in ribosome biogenesis and oxidative stress. However, the roles of SENP3 in cell-cycle regulation remain enigmatic, particularly for oocyte meiotic maturation. Here, we found that SENP3 co-localized with spindles during oocyte meiosis and silencing of SENP3 severely compromised the M phase entry (germinal vesicle breakdown, GVBD) and first polar body extrusion (PBI)...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26151898/inhibition-of-senp3-by-lentivirus-induces-suppression-of-apoptosis-in-experimental-subarachnoid-hemorrhage-in-rats
#18
Yi-Qing Yang, Hua Li, Xiang-Sheng Zhang, Wei Li, Li-Tian Huang, Zhuang Yu, Tian-Wei Jiang, Qiang Chen, Chun-Hua Hang
BACKGROUND: Subarachnoid hemorrhage (SAH) is one of the life-threatening diseases with high morbidity and mortality rates. SUMO-specific proteases 3 (SENP3), a member of the small ubiquitin-like modifier specific protease family, was identified as an isopeptidase that deconjugates SUMOylation (The covalent modification by SUMO) of modified protein substrates. It is reported that SUMO-2/3 conjugation, a member of SUMOylation, presented neuroprotection. The study aimed to evaluate the expression of SENP3 and to explore its potential role in SAH...
October 5, 2015: Brain Research
https://www.readbyqxmd.com/read/26063058/sumoylation-and-ubiquitylation-circuitry-controls-pregnane-x-receptor-biology-in-hepatocytes
#19
Wenqi Cui, Mengxi Sun, Nadezhda Galeva, Todd D Williams, Yoshiaki Azuma, Jeff L Staudinger
Several nuclear receptor (NR) superfamily members are known to be the molecular target of either the small ubiquitin-related modifier (SUMO) or ubiquitin-signaling pathways. However, little is currently known regarding how these two post-translational modifications interact to control NR biology. We show that SUMO and ubiquitin circuitry coordinately modifies the pregnane X receptor (PXR, NR1I2) to play a key role in regulating PXR protein stability, transactivation capacity, and transcriptional repression...
September 2015: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/26046687/psoriatic-t-cells-reduce-epidermal-turnover-time-and-affect-cell-proliferation-contributed-from-differential-gene-expression
#20
Junqin Li, Xinhua Li, Ruixia Hou, Ruifeng Liu, Xincheng Zhao, Feng Dong, Chunfang Wang, Guohua Yin, Kaiming Zhang
Psoriasis is mediated primarily by T cells, which reduce epidermal turnover time and affect keratinocyte proliferation. We aimed to identify differentially expressed genes (DEG) in T cells from normal, five pairs of monozygotic twins concordant or discordant for psoriasis, to determine whether these DEG may account for the influence to epidermal turnover time and keratinocyte proliferation. The impact of T cells on keratinocyte proliferation and epidermal turnover time were investigated separately by immunohistochemistry and cultured with (3) H-TdR...
September 2015: Journal of Dermatology
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