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Deubiquitinase

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https://www.readbyqxmd.com/read/28212404/the-pineal-gland-a-model-for-adrenergic-modulation-of-ubiquitin-ligases
#1
Jerry Vriend, Wenjun Liu, Russel J Reiter
INTRODUCTION: A recent study of the pineal gland of the rat found that the expression of more than 3000 genes showed significant day/night variations (The Hartley dataset). The investigators of this report made available a supplemental table in which they tabulated the expression of many genes that they did not discuss, including those coding for components of the ubiquitin proteasome system. Herein we identify the genes of the ubiquitin proteasome system whose expression were significantly influenced by environmental lighting in the Hartley dataset, those that were stimulated by DBcAMP in pineal glands in culture, and those that were stimulated by norepinephrine...
2017: PloS One
https://www.readbyqxmd.com/read/28202764/trim25-is-required-for-the-antiviral-activity-of-zinc-finger-antiviral-protein-zap
#2
Xiaojiao Zheng, Xinlu Wang, Fan Tu, Qin Wang, Zusen Fan, Guangxia Gao
Zinc-finger antiviral protein (ZAP) is a host factor that specifically inhibits the replication of certain viruses by binding to viral mRNAs, and repressing the translation and/or promoting the degradation of target mRNA. In addition, ZAP regulates the expression of certain cellular genes. Here, we report that tripartite motif-containing protein 25 (TRIM25), a ubiquitin E3 ligase, is required for the antiviral activity of ZAP. Downregulation of endogenous TRIM25 abolished ZAP's antiviral activity. The E3 ligase activity of TRIM25 is required for this regulation...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202673/molecular-architecture-of-polycomb-repressive-complexes
#3
REVIEW
Emily C Chittock, Sebastian Latwiel, Thomas C R Miller, Christoph W Müller
The polycomb group (PcG) proteins are a large and diverse family that epigenetically repress the transcription of key developmental genes. They form three broad groups of polycomb repressive complexes (PRCs) known as PRC1, PRC2 and Polycomb Repressive DeUBiquitinase, each of which modifies and/or remodels chromatin by distinct mechanisms that are tuned by having variable compositions of core and accessory subunits. Until recently, relatively little was known about how the various PcG proteins assemble to form the PRCs; however, studies by several groups have now allowed us to start piecing together the PcG puzzle...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28198400/ubiquitin-c-terminal-hydrolase37-regulates-tcf7-dna-binding-for-the-activation-of-wnt-signalling
#4
Wonhee Han, Hyeyoon Lee, Jin-Kwan Han
The Tcf/Lef family of transcription factors mediates the Wnt/β-catenin pathway that is involved in a wide range of biological processes, including vertebrate embryogenesis and diverse pathogenesis. Post-translational modifications, including phosphorylation, sumoylation and acetylation, are known to be important for the regulation of Tcf/Lef proteins. However, the importance of ubiquitination and ubiquitin-mediated regulatory mechanisms for Tcf/Lef activity are still unclear. Here, we newly show that ubiquitin C-terminal hydrolase 37 (Uch37), a deubiquitinase, interacts with Tcf7 (formerly named Tcf1) to activate Wnt signalling...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198361/dub3-inhibition-suppresses-breast-cancer-invasion-and-metastasis-by-promoting-snail1-degradation
#5
Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana Napier, Qiuying Shi, Jiong Deng, B Mark Evers, Binhua P Zhou
Snail1, a key transcription factor of epithelial-mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196907/acetylation-dependent-regulation-of-mdm2-e3-ligase-activity-dictates-its-oncogenic-function
#6
Naoe T Nihira, Kohei Ogura, Kouhei Shimizu, Brian J North, Jinfang Zhang, Daming Gao, Hiroyuki Inuzuka, Wenyi Wei
Abnormal activation of the oncogenic E3 ubiquitin ligase murine double minute 2 (MDM2) is frequently observed in human cancers. By ubiquitinating the tumor suppressor p53 protein, which leads to its proteasome-mediated destruction, MDM2 limits the tumor-suppressing activity of p53. On the other hand, by ubiquitinating itself, MDM2 targets itself for destruction and promotes the p53 tumor suppressor pathway, a process that can be antagonized by the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP)...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28196299/activity-based-probes-for-the-ubiquitin-conjugation-deconjugation-machinery-new-chemistries-new-tools-and-new-insights
#7
REVIEW
David S Hewings, John A Flygare, Matthew Bogyo, Ingrid E Wertz
The reversible post-translational modification of proteins by ubiquitin and ubiquitin-like proteins regulates almost all cellular processes, by affecting protein degradation, localization, and complex formation. Deubiquitinases (DUBs) are proteases that remove ubiquitin modifications or cleave ubiquitin chains. Most DUBs are cysteine proteases, which makes them well suited for study by activity-based probes. These DUB probes report on deubiquitinase activity by reacting covalently with the active site in an enzyme-catalyzed manner...
February 14, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28187457/the-b-box-module-of-cyld-is-responsible-for-its-intermolecular-interaction-and-cytoplasmic-localization
#8
Songbo Xie, Miao Chen, Siqi Gao, Tao Zhong, Peng Zhou, Dengwen Li, Jun Zhou, Jinmin Gao, Min Liu
The tumor suppressor protein cylindromatosis (CYLD), as a microtubule-associated deubiquitinase, plays a pivotal role in a wide range of cellular activities, including innate immunity, cell division, and ciliogenesis. Structural characterization reveals a small zinc-binding B-box inserted within the ubiquitin specific protease (USP) domain of CYLD; however, the exact role for this module remains yet to be elucidated. Here we identify a critical role for the B-box in facilitating the intermolecular interaction and subcellular localization of CYLD...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28166483/the-importance-of-regulatory-ubiquitination-in-cancer-and-metastasis
#9
L H Gallo, J Ko, D J Donoghue
Ubiquitination serves as a degradation mechanism of proteins, but is involved in additional cellular processes such as activation of NFκB inflammatory response and DNA damage repair. We highlight the E2 ubiquitin conjugating enzymes, E3 ubiquitin ligases and Deubiquitinases that support the metastasis of a plethora of cancers. E3 ubiquitin ligases also modulate pluripotent cancer stem cells attributed to chemotherapy resistance. We further describe mutations in E3 ubiquitin ligases that support tumor proliferation and adaptation to hypoxia...
February 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28157208/rnf20-and-histone-h2b-ubiquitylation-exert-opposing-effects-in-basal-like-versus-luminal-breast-cancer
#10
Ohad Tarcic, Roy Z Granit, Ioannis S Pateras, Hadas Masury, Bella Maly, Yaara Zwang, Yosef Yarden, Vassilis G Gorgoulis, Eli Pikarsky, Ittai Ben-Porath, Moshe Oren
Breast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors...
February 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28154181/usp39-deubiquitinase-is-essential-for-kras-driven-cancer
#11
Julia M Fraile, Eusebio Manchado, Amaia Lujambio, Victor Quesada, Diana Campos-Iglesias, Thomas Webb, Scott W Lowe, Carlos Lopez-Otin, Jose M P Freije
KRAS is the most frequently mutated oncogene in human cancer, but its therapeutic targeting remains challenging. Here, we report a synthetic lethal screen with a library of deubiquitinases and identify USP39, which encodes an essential splicing factor, as a critical gene for the viability of KRAS-dependent cells. We show that splicing fidelity inhibitors decrease preferentially the proliferation rate of KRAS-active cells. Moreover, depletion of DHX38, encoding an USP39-interacting splicing factor, also reduces the viability of these cells...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28151478/proteasome-associated-deubiquitinase-ubiquitin-specific-protease-14-regulates-prostate-cancer-proliferation-by-deubiquitinating-and-stabilizing-androgen-receptor
#12
Yuning Liao, Ningning Liu, Xianliang Hua, Jianyu Cai, Xiaohong Xia, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Androgen receptor (AR) is frequently over-expressed and plays a critical role in the growth and progression of human prostate cancer. The therapy attempting to target AR signalling was established in decades ago but the treatment of prostate cancer is far from being satisfactory. The assignable cause is that our understanding of the mechanism of AR regulation and re-activation remains incomplete. Increasing evidence suggests that deubiquitinases are involved in the regulation of cancer development and progression but the specific underlying mechanism often is not elucidated...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28129647/uncovering-the-role-of-usp54-in-cancer
#13
EDITORIAL
Veronica Miguela, Amaia Lujambio
News on "The deubiquitinase USP54 is overexpressed in colorectal cancer stem cells and promotes intestinal tumorigenesis" by Julia M. Fraile, Oncotarget, 2016; 7(46):74427-74434. doi: 10.18632/oncotarget.12769.
January 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115216/mysm1-deficiency-genotoxic-stress-associated-bone-marrow-failure-and-developmental-aberrations
#14
Ehsan Bahrami, Maximilian Witzel, Tomas Racek, Jacek Puchałka, Sebastian Hollizeck, Naschla Greif-Kohistani, Daniel Kotlarz, Hans-Peter Horny, Regina Feederle, Heinrich Schmidt, Roya Sherkat, Doris Steinemann, Gudrun Göhring, Brigitte Schlegelbeger, Michael H Albert, Waleed Al-Herz, Christoph Klein
BACKGROUND: Myb-Like, SWIRM and MPN domains 1 (MYSM1) is a transcriptional regulator mediating histone deubiquitination. Its role in human immunity and hematopoiesis is poorly understood. OBJECTIVES: To investigate the clinical, cellular and molecular features in two siblings presenting with progressive bone marrow failure, immunodeficiency and developmental aberrations. METHODS: We performed genome-wide homozygosity mapping, whole-exome sequencing (WES) and Sanger sequencing, immunophenotyping studies as well as analysis of genotoxic stress responses...
January 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28108249/synthesis-and-biological-evaluation-of-thiazole-derivatives-as-novel-usp7-inhibitors
#15
Chao Chen, Jiemei Song, Jinzheng Wang, Chang Xu, Caiping Chen, Wei Gu, Hongbin Sun, Xiaoan Wen
Herpesvirus-associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with and stabilizes Mdm2, and represents one of the first examples that deubiquitinases oncogenic proteins. USP7 has been regarded as a potential drug target for cancer therapy. Inhibitors of USP7 have been recently shown to suppress tumor cell growth in vitro and in vivo. Based on leading USP7 inhibitors P5091 and P22077, we designed and synthesized a series of thiazole derivatives. The results of in vitro assays showed that the thiazole compounds exhibited low micromolar inhibition activity against both USP7 enzyme and cancer cell lines...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28103322/htlv-1-tax-induces-formation-of-the-active-macromolecular-ikk-complex-by-generating-lys63-and-met1-linked-hybrid-polyubiquitin-chains
#16
Yuri Shibata, Fuminori Tokunaga, Eiji Goto, Ginga Komatsu, Jin Gohda, Yasushi Saeki, Keiji Tanaka, Hirotaka Takahashi, Tatsuya Sawasaki, Satoshi Inoue, Hiroyuki Oshiumi, Tsukasa Seya, Hiroyasu Nakano, Yuetsu Tanaka, Kazuhiro Iwai, Jun-Ichiro Inoue
The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28098164/uncovering-the-sumoylation-and-ubiquitylation-crosstalk-in-human-cells-using-sequential-peptide-immunopurification
#17
Frédéric Lamoliatte, Francis P McManus, Ghizlane Maarifi, Mounira K Chelbi-Alix, Pierre Thibault
Crosstalk between the SUMO and ubiquitin pathways has recently been reported. However, no approach currently exists to determine the interrelationship between these modifications. Here, we report an optimized immunoaffinity method that permits the study of both protein ubiquitylation and SUMOylation from a single sample. This method enables the unprecedented identification of 10,388 SUMO sites in HEK293 cells. The sequential use of SUMO and ubiquitin remnant immunoaffinity purification facilitates the dynamic profiling of SUMOylated and ubiquitylated proteins in HEK293 cells treated with the proteasome inhibitor MG132...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28096485/murine-cytomegalovirus-deubiquitinase-regulates-viral-chemokine-levels-to-control-inflammation-and-pathogenesis
#18
Adam T Hilterbrand, Daniel R Boutz, Edward M Marcotte, Jason W Upton
: Maintaining control over inflammatory processes represents a paradox for viral pathogens. Although many viruses induce host inflammatory responses to facilitate infection, control is necessary to avoid overactivation. One way is through the manipulation of proinflammatory chemokine levels, both host and viral. Murine cytomegalovirus (MCMV), a model betaherpesvirus, encodes a viral C-C chemokine, MCK2, which promotes host inflammatory responses and incorporates into virions to facilitate viral dissemination...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28091961/-1-h-13-c-and-15-n-backbone-and-side-chain-resonance-assignments-of-the-znf-ubp-domain-of-usp20-vdu2
#19
Yuanyuan Yang, Yi Wen, Naixia Zhang
Deubiquitinase USP20/VDU2 has been identified as a regulator of multiple proteins including hypoxia-inducible factor (HIF)-1α, β2-adrenergic receptor, and tumor necrosis factor receptor associated factor 6 etc. It contains four structural domains, including an N-terminal zinc-finger ubiquitin binding domain (ZnF-UBP) that potentially helps USP20 to recruit its ubiquitin substrates. Here we report the (1)H, (13)C and (15)N backbone and side-chain resonance assignments of the ZnF-UBP domain of USP20/VDU2. The BMRB accession number is 26901...
January 13, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28074857/deubiquitylation-of-hepatitis-b-virus-x-protein-hbx-by-ubiquitin-specific-peptidase-15-usp15-increases-hbx-stability-and-its-transactivation-activity
#20
Zhi-Jun Su, Jia-Shou Cao, Yan-Fang Wu, Wan-Nan Chen, Xinjian Lin, Yun-Li Wu, Xu Lin
Hepatitis B virus X protein (HBx) plays important roles in viral replication and the development of hepatocellular carcinoma. HBx is a rapid turnover protein and ubiquitin-proteasome pathway has been suggested to influence HBx stability as treatment with proteasome inhibitors increases the levels of HBx protein and causes accumulation of the polyubiquitinated forms of HBx. Deubiquitinases (DUBs) are known to act by removing ubiquitin moieties from proteins and thereby reverse their stability and/or activity...
January 11, 2017: Scientific Reports
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