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Deubiquitinase

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https://www.readbyqxmd.com/read/28544703/high-ubiquitin-specific-protease-44-expression-induces-dna-aneuploidy-and-provides-independent-prognostic-information-in-gastric-cancer
#1
Sho Nishimura, Eiji Oki, Koji Ando, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39...
May 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28542437/cp5-system-for-simple-and-highly-efficient-protein-purification-with-a-c-terminal-designed-mini-tag
#2
Hiroyuki Takeda, Wei Zhou, Kohki Kido, Ryoji Suno, Takahiro Iwasaki, Takuya Kobayashi, Tatsuya Sawasaki
There are many strategies to purify recombinant proteins of interest, and affinity purification utilizing monoclonal antibody that targets a linear epitope sequence is one of the essential techniques used in current biochemistry and structural biology. Here we introduce a new protein purification system using a very short CP5 tag. First, we selected anti-dopamine receptor D1 (DRD1) rabbit monoclonal antibody clone Ra62 (Ra62 antibody) as capture antibody, and identified its minimal epitope sequence as a 5-amino-acid sequence at C-terminal of DRD1 (GQHPT-COOH, D1CE sequence)...
2017: PloS One
https://www.readbyqxmd.com/read/28538147/structural-and-functional-investigations-of-the-n-terminal-ubiquitin-binding-region-of-usp25
#3
Yuanyuan Yang, Li Shi, Yiluan Ding, Yanhong Shi, Hong-Yu Hu, Yi Wen, Naixia Zhang
Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28535005/rpn11-deubiquitinase-promotes-proliferation-and-migration-of-breast-cancer-cells
#4
Guoqing Luo, Ningdong Hu, Xu Xia, Jingjing Zhou, Changsheng Ye
The deubiquitinase enzyme RPN11 is involved in oncogenesis in various types of cancer. However, in breast cancer, the expression levels, prognostic relevance and biological function of RPN11 remains unclear. In the present study, RPN11 expression levels in breast cancer tissues and adjacent non‑tumor tissues were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining, and the association of RPN11 with clinicopathological features of breast cancer was evaluated...
May 16, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28524749/ubiquitin-enzymes-in-the-regulation-of-immune-responses
#5
Petra Ebner, Gijs A Versteeg, Fumiyo Ikeda
Ubiquitination plays a central role in the regulation of various biological functions including immune responses. Ubiquitination is induced by a cascade of enzymatic reactions by E1 ubiquitin activating enzyme, E2 ubiquitin conjugating enzyme, and E3 ubiquitin ligase, and reversed by deubiquitinases. Depending on the enzymes, specific linkage types of ubiquitin chains are generated or hydrolyzed. Because different linkage types of ubiquitin chains control the fate of the substrate, understanding the regulatory mechanisms of ubiquitin enzymes is central...
May 19, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28515325/mutual-regulation-between-polo-like-kinase-3-and-siah2-e3-ubiquitin-ligase-defines-a-regulatory-network-that-fine-tunes-the-cellular-response-to-hypoxia-and-nickel
#6
Cen Li, Soyoung Park, Xiaowen Zhang, Wei Dai, Dazhong Xu
Elevated cellular response to hypoxia, which contributes to cell transformation and tumor progression, is a prominent feature of malignant cells in solid tumors. Polo-like kinase 3 (Plk3) is a serine/threonine protein kinase known to inhibit the cellular response to hypoxia and tumorigenesis. Nickel compounds are well established human carcinogens that induce tumorigenesis partly through their hypoxia-mimicking effects. Despite the previous research efforts, the role of Plk3 in the hypoxic response induced by hypoxia or nickel is not completely understood...
May 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506875/deubiquitinase-usp33-is-negatively-regulated-by-%C3%AE-trcp-through-ubiquitin-dependent-proteolysis
#7
Qiao Cheng, Yukang Yuan, Lemin Li, Tingting Guo, Ying Miao, Ying Ren, Jin Liu, Qian Feng, Xiaofang Wang, Peng Zhao, Yibo Zuo, Liping Qian, Liting Zhang, Hui Zheng
Ubiquitin-mediated proteolysis regulates cellular levels of various proteins, and therefore plays important roles in controlling cell signaling and disease progression. The Skp1-Cul1-F-box ubiquitin ligase β-TrCP is recognized as an important negative regulator for numerous key signaling proteins. Recently, the deubiquitinases (DUBs) have turned out to be essential to regulate signaling pathways related to human diseases. However, whether β-TrCP is able to regulate the deubiquitinase family members remains largely unexplored...
May 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28502290/deubiquitinase-yod1-the-potent-activator-of-yap-in-hepatomegaly-and-liver-cancer
#8
Youngeun Kim, Eek-Hoon Jho
The advances of our understanding in the Hippo signaling as a key regulatory pathway of proliferation and apoptosis have provided mechanical insights for controlling organ size and tumorigenicity. Recently, much attention was given to the regulation of LATS1/2 (large tumor suppressor) kinases that phosphorylate YAP/TAZ, a transcriptional co-activator in the Hippo pathway, and control the level and nuclear localization of YAP/TAZ. In our recent work, we showed that deubiquitinase YOD1 stabilizes ITCH and facilitates ITCH-mediated LATS1/2 ubiquitination and degradation, which results in increased YAP/TAZ level...
May 15, 2017: BMB Reports
https://www.readbyqxmd.com/read/28500221/ubiquitin-c-terminal-hydrolase-l1-uch-l1-promotes-hippocampus-dependent-memory-via-its-deubiquitinating-effect-on-trkb
#9
Yun-Yun Guo, Lu Yi, Yuan Zheng, Xiao-Rong Chen, Jun-Lu Dong, Rong-Rong Yuan, Shu-Hong Huang, Hui Yu, Yue Wang, Zhe-Yu Chen, Bo Su
Multiple studies have established that brain-derived neurotrophic factor (BDNF) plays a critical role in the regulation of synaptic plasticity via its receptor TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological functions remain poorly understood. In this study, we demonstrate that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning (CFC) learning and memory via the regulation of ubiquitination of TrkB...
May 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28498721/mechanisms-of-deubiquitinase-specificity-and-regulation
#10
Tycho E T Mevissen, David Komander
Protein ubiquitination is one of the most powerful posttranslational modifications of proteins, as it regulates a plethora of cellular processes in distinct manners. Simple monoubiquitination events coexist with more complex forms of polyubiquitination, the latter featuring many different chain architectures. Ubiquitin can be subjected to further posttranslational modifications (e.g., phosphorylation and acetylation) and can also be part of mixed polymers with ubiquitin-like modifiers such as SUMO (small ubiquitinrelated modifier) or NEDD8 (neural precursor cell expressed, developmentally downregulated 8)...
May 12, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28497808/a-unique-deubiquitinase-that-deconjugates-phosphoribosyl-linked-protein-ubiquitination
#11
Jiazhang Qiu, Kaiwen Yu, Xiaowen Fei, Yao Liu, Ernesto S Nakayasu, Paul D Piehowski, Jared B Shaw, Kedar Puvar, Chittaranjan Das, Xiaoyun Liu, Zhao-Qing Luo
Ubiquitination regulates many aspects of host immunity and thus is a common target for infectious agents. Recent studies have revealed that members of the SidE effector family of the bacterial pathogen Legionella pneumophila attack several small GTPases associated with the endoplasmic reticulum by a novel ubiquitination mechanism that does not require the E1 and E2 enzymes of the host ubiquitination machinery. In this case, ubiquitin is first activated by ADP-ribosylation at Arg42 by a mono-ADP-ribosyltransferase activity; the intermediate is then cleaved by a phosphodiesterase activity also residing within SdeA, concomitant with the attachment of ubiquitin to serine residues of substrate proteins via a phosphoribosyl linker...
May 12, 2017: Cell Research
https://www.readbyqxmd.com/read/28492230/targeting-the-deubiquitinase-stambp-inhibits-nalp7-inflammasome-activity
#12
Joseph S Bednash, Nathaniel Weathington, James Londino, Mauricio Rojas, Dexter L Gulick, Robert Fort, SeungHye Han, Alison C McKelvey, Bill B Chen, Rama K Mallampalli
Inflammasomes regulate innate immune responses by facilitating maturation of inflammatory cytokines, interleukin (IL)-1β and IL-18. NACHT, LRR and PYD domains-containing protein 7 (NALP7) is one inflammasome constituent, but little is known about its cellular handling. Here we show a mechanism for NALP7 protein stabilization and activation of the inflammasome by Toll-like receptor (TLR) agonism with bacterial lipopolysaccharide (LPS) and the synthetic acylated lipopeptide Pam3CSK4. NALP7 is constitutively ubiquitinated and recruited to the endolysosome for degradation...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28490584/a-naturally-occurring-recombinant-enterovirus-expresses-a-torovirus-deubiquitinase
#13
Pengcheng Shang, Saurav Misra, Ben Hause, Ying Fang
Enteroviruses are implicated in a wide range of diseases in human and animals. In this study, a novel enterovirus (species G; EVG 08/NC_USA/2015) was isolated from a diagnostic sample of neonatal pig diarrhea case and identified using metagenomics and complete genome sequencing. The viral genome shares 75.4% nucleotide identity with a prototypic EVG strain (PEV9 UKG/410/73). Remarkably, a 582 nucleotide insertion, flanked by 3C(pro) cleavage sites at 5' - and 3' - ends, was found in the 2C/3A junction region of the viral genome...
May 10, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28489822/traf2-and-otud7b-govern-a-ubiquitin-dependent-switch-that-regulates-mtorc2-signalling
#14
Bin Wang, Zuliang Jie, Donghyun Joo, Alban Ordureau, Pengda Liu, Wenjian Gan, Jianping Guo, Jinfang Zhang, Brian J North, Xiangpeng Dai, Xuhong Cheng, Xiuwu Bian, Lingqiang Zhang, J Wade Harper, Shao-Cong Sun, Wenyi Wei
The mechanistic target of rapamycin (mTOR) has a key role in the integration of various physiological stimuli to regulate several cell growth and metabolic pathways. mTOR primarily functions as a catalytic subunit in two structurally related but functionally distinct multi-component kinase complexes, mTOR complex 1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated with a variety of human diseases, including metabolic disorders and cancer. Thus, both mTORC1 and mTORC2 kinase activity is tightly controlled in cells...
May 10, 2017: Nature
https://www.readbyqxmd.com/read/28489002/usp5-leon-deubiquitinase-confines-postsynaptic-growth-by-maintaining-ubiquitin-homeostasis-through-ubiquilin
#15
Chien-Hsiang Wang, Yi-Chun Huang, Pei-Yi Chen, Ying-Ju Cheng, Hsiu-Hua Kao, Haiwei Pi, Cheng-Ting Chien
Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant...
May 10, 2017: ELife
https://www.readbyqxmd.com/read/28484036/bam-dependent-deubiquitinase-complex-can-disrupt-germ-line-stem-cell-maintenance-by-targeting-cyclin-a
#16
Shanming Ji, Chaoyi Li, Lin Hu, Kehui Liu, Jie Mei, Yuewan Luo, Yi Tao, Zongping Xia, Qinmiao Sun, Dahua Chen
Drosophila germ-line stem cells (GSCs) provide an excellent model to study the regulatory mechanisms of stem cells in vivo. Bag of marbles (bam) has been demonstrated to be necessary and sufficient to promote GSC and cystoblast differentiation. Despite extensive investigation of its regulation and genetic functions, the biochemical nature of the Bam protein has been unknown. Here, we report that Bam is an ubiquitin-associated protein and controls the turnover of cyclin A (CycA). Mechanistically, we found that Bam associated with Otu to form a deubiquitinase complex that stabilized CycA by deubiquitination, thus providing a mechanism to explain how ectopic expression of Bam in GSCs promotes differentiation...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28483520/pppde1-is-a-novel-deubiquitinase-belonging-to-a-cysteine-isopeptidase-family
#17
Xingwang Xie, Xueyan Wang, Dong Jiang, Jianghua Wang, Ran Fei, Xu Cong, Lai Wei, Yu Wang, Hongsong Chen
Ubiquitinlation of proteins is prevalent and important in both normal and pathological cellular processes. Deubiquitinating enzymes (DUBs) can remove the ubiquitin tags on substrate proteins and dynamically regulate the ubiquitination process. The PPPDE family proteins were predicted to be a novel class of deubiquitinating peptidase, but this has not yet been experimentally proved. Here we validated the deubiquitinating activity of PPPDE1 and revealed its isopeptidase activity against ubiquitin conjugated through Lys 48 and Lys 63...
May 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28481361/linear-ubiquitination-of-cytosolic-salmonella-typhimurium-activates-nf-%C3%AE%C2%BAb-and-restricts-bacterial-proliferation
#18
Sjoerd J L van Wijk, Franziska Fricke, Lina Herhaus, Jalaj Gupta, Katharina Hötte, Francesco Pampaloni, Paolo Grumati, Manuel Kaulich, Yu-Shin Sou, Masaaki Komatsu, Florian R Greten, Simone Fulda, Mike Heilemann, Ivan Dikic
Ubiquitination of invading Salmonella Typhimurium triggers autophagy of cytosolic bacteria and restricts their spread in epithelial cells. Ubiquitin (Ub) chains recruit autophagy receptors such as p62/SQSTM1, NDP52/CALCOCO and optineurin (OPTN), which initiate the formation of double-membrane autophagosomal structures and lysosomal destruction in a process known as xenophagy. Besides this, the functional consequences and mechanistic regulation of differentially linked Ub chains at the host-Salmonella interface have remained unexplored...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28476333/identification-of-4-arylidene-curcumin-analogues-as-novel-proteasome-inhibitors-for-potential-anticancer-agents-targeting-19s-regulatory-particle-associated-deubiquitinase
#19
Xin Yue, Yinglin Zuo, Hongpeng Ke, Jiaming Luo, Lanlan Lou, Wenjing Qin, Youqiao Wang, Ziyi Liu, Daoyuan Chen, Haixia Sun, Weichao Zheng, Cuige Zhu, Ruimin Wang, Gesi Wen, Jun Du, Binhua Zhou, Xianzhang Bu
The proteasomal 19S regulatory particle (RP) associated deubiquitinases (DUBs) have attracted much attention owing to its potential as a therapeutic target for cancer therapy. Identification of new entities against 19S RP associated DUBs and illustration of the underlying mechanisms is crucial for discovery of novel proteasome blockers. In this study, a series of 4-arylidene curcumin analogues were identified as potent proteasome inhibitor by preferentially blocking deubiquitinase function of proteasomal 19S RP with moderate 20S CP inhibition...
May 2, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28475898/molecular-mechanism-of-substrate-processing-by-the-cdc48-atpase-complex
#20
Nicholas O Bodnar, Tom A Rapoport
The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding...
May 4, 2017: Cell
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