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Deubiquitination

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https://www.readbyqxmd.com/read/28724765/translesion-polymerase-pol-%C3%AE-is-required-for-efficient-epstein-barr-virus-infectivity-and-is-regulated-by-the-viral-deubiquitinating-enzyme-bplf1
#1
Ossie F Dyson, Joseph S Pagano, Christopher B Whitehurst
Epstein-Barr Virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. Previously we showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis pathway (TLS), a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument indicating that BPLF1 may function both early and late during infection. BPLF1 expresses deubiquitinating activity that is strictly conserved across the Herpesviridae; mutation of the active-site cysteine results in loss of enzymatic activity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28722507/polyglutamine-tracts-regulate-autophagy
#2
Avraham Ashkenazi, Carla F Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C Hardenberg, Sara Imarisio, Fiona M Menzies, David C Rubinsztein
Expansions of polyglutamine (polyQ) tracts in different proteins cause 9 neurodegenerative conditions, such as Huntington disease and various ataxias. However, many normal mammalian proteins contain shorter polyQ tracts. As these are frequently conserved in multiple species, it is likely that some of these polyQ tracts have important but unknown biological functions. Here we review our recent study showing that the polyQ domain of the deubiquitinase ATXN3/ataxin-3 enables its interaction with BECN1/beclin 1, a key macroautophagy/autophagy initiator...
July 19, 2017: Autophagy
https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#3
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28718215/usp18-protects-against-hepatic-steatosis-and-insulin-resistance-via-its-dub-activity
#4
Shimin An, Ling-Ping Zhao, Li-Jun Shen, Siyuan Wang, Kuo Zhang, Yu Qi, Jilin Zheng, Xiao-Jing Zhang, Xue-Yong Zhu, Rong Bao, Ling Yang, Yue-Xin Lu, Zhi-Gang She, Yi-Da Tang
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity and chronic low-grade inflammation. However, the pathogenic mechanism of NAFLD is poorly understood, which hinders the exploration of possible treatments. Here, we first report that ubiquitin-specific protease 18 (USP18), a member of the deubiquitinating (DUB) enzyme family, plays regulatory roles in NAFLD progression. The expression of USP18 was down-regulated in the livers of non-alcoholic steatohepatitis (NASH) patients and high-fat diet (HFD) induced or genetically obese mice...
July 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28703681/activation-of-gene-expression-by-histone-deubiquitinase-otld1
#5
Ido Keren, Vitaly Citovsky
One of the main mechanisms of epigenetic control is post translational modification of histones, and one of the relatively less characterized, yet functionally important histone modifications is monoubiquitylation, which is reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a transcriptional repressor. But, could the same deubiquitinase act both as a repressor and an activator? Here, we addressed this question...
July 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28701375/spata2-regulates-the-activation-of-ripk1-by-modulating-linear-ubiquitination
#6
Ran Wei, Lily Wen Xu, Jianping Liu, Yanxia Li, Pei Zhang, Bing Shan, Xiaojuan Lu, Lihui Qian, Zheming Wu, Kangyun Dong, Hong Zhu, Lifeng Pan, Junying Yuan, Heling Pan
Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD (cylindromatosis)...
July 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28695315/ubiquitin-specific-proteases-function-in-plant-development-and-stress-responses
#7
REVIEW
Huapeng Zhou, Jinfeng Zhao, Jingqing Cai, Suyash B Patil
UBIQUITIN-SPECIFIC PROTEASES play important roles in plant development and stress responses. Protein ubiquitination and deubiquitination are reversible processes, which can modulate the stability, activity as well as subcellular localization of the substrate proteins. UBIQUITIN-SPECIFIC PROTEASE (UBP) protein family participates in protein deubiquitination. Members of UBP family are involved in a variety of physiological processes in plants, as evidenced by their functional characterization in model plant Arabidopsis and other plants...
July 10, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/28681694/uchl5-expression-associates-with-improved-survival-in-lymph-node-positive-rectal-cancer
#8
Leena Arpalahti, Jaana Hagström, Harri Mustonen, Mikael Lundin, Caj Haglund, Carina I Holmberg
Colorectal cancer is among the three most common cancer types for both genders, with a rising global incidence. To date, prognostic evaluation is difficult and largely dependent on early detection and successful surgery. UCHL5/Uch37 is an integral part of the protein homeostasis network as one of the three deubiquitinating enzymes associated with the 26S proteasome. Here, we have investigated in colorectal cancer the possible association of UCHL5 tumor expression and patient survival. UCHL5 tumor expression was evaluated by immunohistochemistry in 779 surgically treated colorectal cancer patients from Helsinki University Hospital, Finland, with assessment of clinicopathological parameters and the effect of UCHL5 expression on patient survival...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28669576/histone-h2a-monoubiquitination-in-neurodevelopmental-disorders
#9
REVIEW
Anshika Srivastava, Brian McGrath, Stephanie L Bielas
Covalent histone modifications play an essential role in gene regulation and cellular specification required for multicellular organism development. Monoubiquitination of histone H2A (H2AUb1) is a reversible transcriptionally repressive mark. Exchange of histone H2A monoubiquitination and deubiquitination reflects the succession of transcriptional profiles during development required to produce cellular diversity from pluripotent cells. Germ-line pathogenic variants in components of the H2AUb1 regulatory axis are being identified as the genetic basis of congenital neurodevelopmental disorders...
June 29, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28662510/the-deubiquitinating-enzyme-usp14-regulates-leukemic-chemotherapy-drugs-induced-cell-apoptosis-by-suppressing-ubiquitination-of-aurora-kinase-b
#10
Chunge Song, Ruojin Ma, Xiaoyu Yang, Sulei Pang
BACKGROUND/AIMS: Aurora kinase B is a mitotic checkpoint kinase that plays a pivotal role in mitosis by ensuring correct chromosome segregation and normal progression through mitosis. Aurora B has been found to be amplified and overexpressed in several types of leukemia. The deubiquitinating enzyme USP14 is one of three proteasome-associated deubiquitinating enzymes and plays critical roles in diverse biological processes including cancer. However, whether USP14 has a role in leukemia cells remains elusive...
June 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28655758/ubiquitin-specific-peptidase-7-usp7-mediated-deubiquitination-of-the-histone-deacetylase-sirt7-regulates-gluconeogenesis
#11
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 (HDACs), 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...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28653876/nuclear-ubiquitin-c-terminal-hydrolase-l5-expression-associates-with-increased-patient-survival-in-pancreatic-ductal-adenocarcinoma
#12
Leena Arpalahti, Kapo Saukkonen, Jaana Hagström, Harri Mustonen, Hanna Seppänen, Caj Haglund, Carina I Holmberg
Pancreatic ductal adenocarcinoma is a lethal disease with an overall 5-year survival of less than 5%. Prognosis among surgically treated patients is difficult and identification of new biomarkers is essential for accurate prediction of patient outcome. As part of one of the major cellular protein degradation systems, the proteasome plays a fundamental role in both physiological and pathophysiological conditions including cancer. The proteasome-associated deubiquitinating enzyme ubiquitin C-terminal hydrolase L5 (UCHL5)/Uch37 is a modulator of proteasome activity with cancer prognostic marker potential...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28635516/concentration-of-uhcl1-in-the-serum-of-children-with-acute-appendicitis-before-and-after-surgery-and-its-correlation-with-crp-and-prealbumin
#13
Ewa Matuszczak, Marzena Tylicka, Wojciech Dębek, Anna Tokarzewicz, Ewa Gorodkiewicz, Adam Hermanowicz
Ubiquitin-mediated protein degradation plays a crucial role in various cellular processes, including signal transduction, cell differentiation, and stress response. Ubiquitin C-terminal hydrolase 1 (UCHL1) is a unique deubiquitinating enzyme that has both hydrolase and ligase activities. The aim of this study was the determination of UCHL1 concentration in serum of children with appendicitis, before and after the surgery. MATERIAL AND METHODS: 42 children with acute appendicitis, who were managed at the Pediatric Surgery Department, between 2013 and 2014, were randomly included into the study (age 9 months up to 14 years, mean age 2...
February 27, 2017: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
https://www.readbyqxmd.com/read/28633009/rna-interference-reveals-the-coregulatory-effects-of-cylindromatosis-on-apoptosis-and-necroptosis-of-photoreceptor-cells-in-experimental-retinal-detachment
#14
Kai Dong, Linfeng Han, Jingwen Liu, Fenghua Wang, Xiaodong Sun
Inhibiting only cell apoptosis or necroptosis in photoreceptor cells does not protect them against death after traumatic retinal detachment. This study was designed to evaluate the coregulatory effects of the deubiquitinating enzyme cylindromatosis on the apoptosis and necroptosis of photoreceptor cells in experimental retinal detachment. Lentivirus Cyld shRNA was generated and used to suppress cylindromatosis expression in Sprague-Dawley rats. Three weeks after injection of lentivirus Cyld shRNA, retinal detachment surgery was performed...
June 17, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28626083/cellular-and-disease-functions-of-the-prader-willi-syndrome-gene-magel2
#15
REVIEW
Klementina Fon Tacer, Patrick Ryan Potts
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme...
June 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#16
Boren Lin, Qi Ke, Haiying Li, Nichole S Pheifer, David C Velliquette, Douglas W Leaman
The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles...
June 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28625850/structure-and-function-of-viral-deubiquitinating-enzymes
#17
REVIEW
Ben A Bailey-Elkin, Robert C M Knaap, Marjolein Kikkert, Brian L Mark
Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication...
June 16, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28621941/sulawesins-a-c-furanosesterterpene-tetronic-acids-that-inhibit-usp7-from-a-psammocinia-sp-marine-sponge
#18
Ahmed H Afifi, Ippei Kagiyama, Ahmed H El-Desoky, Hikaru Kato, Remy E P Mangindaan, Nicole J de Voogd, Nagwa M Ammar, Mohammed S Hifnawy, Sachiko Tsukamoto
Three new furanosesterterpene tetronic acids, sulawesins A-C (1-3), were isolated from a Psammocinia sp. marine sponge, along with the known compounds ircinins-1 (4) and -2 (5). Although ircinins-1 and -2 were previously isolated as (+)- or (-)-enantiomers from marine sponges, we isolated them as enantiomeric mixtures. Sulawesins A and B possess a new carbon skeleton with a 5-(furan-3-yl)-4-hydroxycyclopent-2-enone moiety and were also found to be diastereomeric mixtures of four isomers by an HPLC analysis with a chiral-phase column...
June 16, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28621888/wide-and-thick-grain-1-which-encodes-an-otubain-like-protease-with-deubiquitination-activity-influences-grain-size-and-shape-in-rice
#19
Ke Huang, Dekai Wang, Penggen Duan, Baolan Zhang, Ran Xu, Na Li, Yunhai Li
Grain size and shape are two crucial traits that influence grain yield and grain appearance in rice. Although several factors that affect grain size have been described in rice, the molecular mechanisms underlying grain size and shape determination are still elusive. In this study, we report that the WIDE AND THICK GRAIN 1 (WTG1) functions as an important factor that determines grain size and shape in rice. The wtg1-1 mutant exhibits wide, thick, short and heavy grains and also shows the increased grain number per panicle...
June 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28619731/usp25-regulates-wnt-signaling-by-controlling-the-stability-of-tankyrases
#20
Daichao Xu, Jianping Liu, Tao Fu, Bing Shan, Lihui Qian, Lifeng Pan, Junying Yuan
Aberrant activation of the Wnt signaling pathway plays an important role in human cancer development. Wnt signaling is negatively regulated by Axin, a scaffolding protein that controls a rate-limiting step in the destruction of β-catenin, the central activator of the Wnt pathway. In Wnt-stimulated cells, Axin is rapidly modified by tankyrase-mediated poly(ADP-ribosyl)ation, which promotes the proteolysis of Axin and consequent stabilization of β-catenin. Thus, regulation of the levels and activity of tankyrases is mechanistically important in controlling Wnt signaling...
May 15, 2017: Genes & Development
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