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Deubiquitinase

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https://www.readbyqxmd.com/read/28815021/toward-an-understanding-of-the-cdc48-p97-atpase
#1
REVIEW
Nicholas Bodnar, Tom Rapoport
A conserved AAA+ ATPase, called Cdc48 in yeast and p97 or VCP in metazoans, plays an essential role in many cellular processes by segregating polyubiquitinated proteins from complexes or membranes. For example, in endoplasmic reticulum (ER)-associated protein degradation (ERAD), Cdc48/p97 pulls polyubiquitinated, misfolded proteins out of the ER and transfers them to the proteasome. Cdc48/p97 consists of an N-terminal domain and two ATPase domains (D1 and D2). Six Cdc48 monomers form a double-ring structure surrounding a central pore...
2017: F1000Research
https://www.readbyqxmd.com/read/28808321/the-proteasome-deubiquitinase-inhibitor-b-ap15-enhances-dr5-activation-induced-apoptosis-through-stabilizing-dr5
#2
You-Take Oh, Liang Deng, Jiusheng Deng, Shi-Yong Sun
b-AP15 and its derivatives block proteasome deubiquitinase (DUB) activity and have been developed and tested in the clinic as potential cancer therapeutic agents. b-AP15 induces apoptosis in cancer cells, but the underlying mechanisms are largely undefined. The current study focuses on studying the modulatory effects of b-AP15 on death receptor 5 (DR5) levels and DR5 activation-induced apoptosis as well as on understanding the underlying mechanisms. Treatment with b-AP15 potently increased DR5 levels including cell surface DR5 in different cancer cell lines with limited or no effects on the levels of other related proteins including DR4, c-FLIP, FADD, and caspase-8...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807825/usp3-stabilizes-p53-protein-through-its-deubiquitinase-activity
#3
Song Fu, Shize Shao, Longqiang Wang, Haijun Liu, Haitao Hou, Yanan Wang, Huan Wang, Xiangpeng Huang, Renhua Lv
p53 is the guardian of the genome integrity and the degradation of p53 protein is mediated by MDM2. Here we report that USP3 interacts with p53 and regulates p53 stability. Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation. Reconstitution of wildtype USP3, but not the USP3 C168S mutant, restored the stability of p53 protein and inhibited cell proliferation and transformation. These findings suggest that USP3 is an important regulator of p53 and regulates normal cell transformation...
August 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28807012/protein-deubiquitinase-usp7-is-required-for-osteogenic-differentiation-of-human-adipose-derived-stem-cells
#4
Yiman Tang, Longwei Lv, Wenyue Li, Xiao Zhang, Yong Jiang, Wenshu Ge, Yongsheng Zhou
BACKGROUND: Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with self-renewal capabilities and multilineage differentiation potential, including osteogenesis. Although protein deubiquitinases have been linked to stem cell fate determination, whether protein deubiquitination contributes to lineage commitment during osteogenic differentiation of hASCs remains to be investigated. The objective of this study was to evaluate the effects of the ubiquitin specific protease 7 (USP7) on osteogenic differentiation of hASCs...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28776570/non-canonical-regulation-of-spl-transcription-factors-by-a-human-otub1-like-deubiquitinase-defines-a-new-plant-type-rice-associated-with-higher-grain-yield
#5
Shuansuo Wang, Kun Wu, Qian Qian, Qian Liu, Qi Li, Yajun Pan, Yafeng Ye, Xueying Liu, Jing Wang, Jianqing Zhang, Shan Li, Yuejin Wu, Xiangdong Fu
Achieving increased grain productivity has long been the overriding focus of cereal breeding programs. The ideotype approach has been used to improve rice yield potential at the International Rice Research Institute and in China. However, the genetic basis of yield-related traits in rice remains unclear. Here, we show that a major quantitative trait locus, qNPT1, acts through the determination of a 'new plant type' (NPT) architecture characterized by fewer tillers, sturdier culms and larger panicles, and it encodes a deubiquitinating enzyme with homology to human OTUB1...
August 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28771803/a20-restores-phorbol-ester-induced-differentiation-of-thp-1-cells-in-the-absence-of-nuclear-factor-%C3%AE%C2%BAb-activation
#6
Miho Osako, Momoe Itsumi, Haruka Yamaguchi, Hiroaki Takeuchi, Shoji Yamaoka
A20, also referred to as tumor necrosis factor alpha (TNFα)-induced protein 3 (TNFAIP3), is an ubiquitin-editing enzyme whose expression is enhanced by NF-κB activation, and plays an important role in silencing NF-κB activity. Another well-known role for A20 is to protect cells from TNFα-induced apoptosis. Depletion of NF-κB in differentiating U937 monocytic leukemia cells is known to cause apoptotic cell death; however, much remains to be explored about the molecules that are expressed in an NF-κB-dependent manner and which support monocyte-macrophage differentiation...
August 3, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28768733/central-catalytic-domain-of-brap-rnf52-recognizes-the-types-of-ubiquitin-chains-and-utilizes-oligo-ubiquitin-for-ubiquitylation
#7
Shisako Shoji, Kazuharu Hanada, Noboru Ohsawa, Mikako Shirouzu
RING-finger protein 52 (RNF52), an E3 ubiquitin ligase, is found in eukaryotes from yeast to humans. Human RNF52 is known as breast cancer type 1 susceptibility protein-associated protein 2 (BRAP or BRAP2). The central catalytic domain of BRAP comprises four subdomains: nucleotide-binding α/β plait (NBP), really interesting new gene zinc finger (RING), deubiquitinase-like zinc finger (ZfUBP), and coiled-coil (CC). This domain architecture is conserved in RNF52 orthologs; however, the domain's function in the ubiquitin system has not been delineated...
August 2, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28767417/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#8
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28765887/down-regulation-of-long-noncoding-rna-rp11-713b9-1-contributes-to-the-cell-viability-in-non%C3%A2-small-cell-lung-cancer-nsclc
#9
Jun Cai, Xuan Wang, Hu Huang, Meng Wang, Zhihong Zhang, Yan Hu, Shihua Yu, Yonghua Yang, Jiyuan Yang
Early diagnosis is essential to reduce lung cancer-associated morbidity and mortality rates; however the lack of diagnostic biomarkers for lung cancer has made this difficult. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) serve important roles in cancer occurrence and progression. The present study investigated the novel lncRNA RP11‑713B9.1, which is the antisense transcript of tumor suppressor in lung cancer 1 (TSLC1). The expression levels of RP11‑713B9.1 and TSLC1 in non‑small cell lung cancer were determined using reverse‑transcription quantitative polymerase chain reaction, which revealed that the expression of RP11‑713B9...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28755289/downregulation-of-usp4-promotes-activation-of-microglia-and-subsequent-neuronal-inflammation-in-rat-spinal-cord-after-injury
#10
Xingjie Jiang, Mingchen Yu, Yiqing Ou, Yong Cao, Yu Yao, Ping Cai, Feng Zhang
NF-κB is involved in the activation of microglia, which induces secondary spinal cord injury (SCI). This process involves the activation of NF-κB signaling pathway by TRAF6 through its polyubiquitination function. We know that deubiquitination of TRAF6 mediated by deubiquitinating enzyme (DUB) significantly inhibits activation of NF-κB pathway. The ubiquitin-specific protease 4 (USP4) belongs to the deubiquitinase family. Therefore, we hypothesize that USP4 is involved in the microglial activation and subsequent neuronal inflammation after SCI...
July 28, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28751569/cyld-deubiquitinates-nicotinamide-adenine-dinucleotide-phosphate-oxidase-4-contributing-to-adventitial-remodeling
#11
Bing Yu, Ziyi Liu, Yi Fu, Yingbao Wang, Lu Zhang, Zeyu Cai, Fang Yu, Xian Wang, Jun Zhou, Wei Kong
OBJECTIVE: Transdifferentiation of adventitial fibroblasts (AFs) into myofibroblasts plays a critical role during the vascular remodeling that occurs during atherosclerosis, restenosis, and aortic aneurysm. The ubiquitination/deubiquitination regulatory system is essential for the quality control of proteins. The involvement of ubiquitination/deubiquitination during AF transdifferentiation remains largely unknown. In this study, we determined the role of cylindromatosis (CYLD), a deubiquitinase, in the process of AF differentiation and activation in vitro and in vivo...
July 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28737031/ubiquitin-chain-enrichment-middle-down-mass-spectrometry-ubichem-ms-reveals-cell-cycle-dependent-formation-of-lys11-lys48-branched-ubiquitin-chains
#12
Ambar S J B Rana, Ying Ge, Eric R Strieter
The dynamics of cellular signaling events are tightly regulated by a diverse set of ubiquitin chains. Recent work has suggested that branched ubiquitin chains composed of Lys11 and Lys48 isopeptide linkages play a critical role in regulating cell cycle progression. Yet, endogenous Lys11/Lys48 branched chains could not be detected. By combining a Lys11 linkage specific antibody with high-resolution middle-down mass spectrometry (an approach termed UbiChEM-MS) we sought to identify endogenous Lys11/Lys48 branched ubiquitin chains in cells...
August 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28722507/polyglutamine-tracts-regulate-autophagy
#13
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/28705854/targeting-deubiquitinases-in-cll
#14
Deepa Sampath
No abstract text is available yet for this article.
July 13, 2017: Blood
https://www.readbyqxmd.com/read/28703681/activation-of-gene-expression-by-histone-deubiquitinase-otld1
#15
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
#16
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)...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28688920/single-cell-rna-sequencing-reveals-an-altered-gene-expression-pattern-as-a-result-of-crispr-cas9-mediated-deletion-of-gene-33-mig6-and-chronic-exposure-to-hexavalent-chromium-in-human-lung-epithelial-cells
#17
Soyoung Park, Xiaowen Zhang, Cen Li, Changhong Yin, Jiangwei Li, John T Fallon, Weihua Huang, Dazhong Xu
Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear. In the present study, we used single-cell RNA sequencing to compare gene expression profiles between BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI) with or without CRISPR/cas9-mediated deletion of Gene 33...
September 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28682311/platinum-pyrithione-induces-apoptosis-in-chronic-myeloid-leukemia-cells-resistant-to-imatinib-via-dub-inhibition-dependent-caspase-activation-and-bcr-abl-downregulation
#18
Xiaoying Lan, Chong Zhao, Xin Chen, Peiquan Zhang, Dan Zang, Jinjie Wu, Jinghong Chen, Huidan Long, Li Yang, Hongbiao Huang, Xuejun Wang, Xianping Shi, Jinbao Liu
Chronic myelogenous leukemia (CML) is characterized by the chimeric tyrosine kinase Bcr-Abl. T315I Bcr-Abl is the most notorious point mutation to elicit acquired resistance to imatinib (IM), leading to poor prognosis. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that platinum pyrithione (PtPT) potently inhibits the ubiquitin-proteasome system (UPS) via targeting the 26 S proteasome-associated deubiquitinases (DUBs), without effecting on the 20 S proteasome...
July 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#19
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28670958/usp17-is-upregulated-in-osteosarcoma-and-promotes-cell-proliferation-metastasis-and-epithelial-mesenchymal-transition-through-stabilizing-smad4
#20
Chenyang Song, Wenge Liu, Jiandong Li
USP17 is upregulated in several cancers, indicating that USP17 might play essential functions in tumor development. However, the function of USP17 in osteosarcoma is still unknown. Our work aimed to investigate the function of USP17 in osteosarcoma. We found that the expression of USP17 was upregulated in osteosarcoma tissues and cell lines, including MG-63 and U2OS. Several functional experiments, such as colony formation analysis, Cell Counting Kit-8 assay, wound healing analysis, and transwell assay, showed that USP17 promoted cell proliferation, migration, and invasion...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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