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Ubiquitin-specific protease

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https://www.readbyqxmd.com/read/28938551/overexpression-of-ubiquitin-specific-proteases-44-promotes-the-malignancy-of-glioma-by-stabilizing-tumor-promoter-securin
#1
Yongxiang Zou, Guanzhong Qiu, Lei Jiang, Zheng Cai, Wei Sun, Hongkang Hu, Chengyin Lu, Weilin Jin, Guohan Hu
Ubiquitin specific peptidase 44 (USP44) has been identified as an important component of spindle assemble checkpoint (SAC) to prevent the formation of aneuploidy. However, recent study raised a controversy about the effect of USP44 in tumor. Here, we first confirmed the intranuclear localization of USP44 by testing several specific antibodies to recognize endogenous USP44. Then, data from IHC and qRT-PCR assay indicated that the high expression of USP44 existed in high-grade glioma tissues and signified a poor prognosis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28930533/53bp1-a-guardian-for-centrosomal-integrity
#2
Haeyoung Kim, Hyungshin Yim
53BP1 is known as a mediator in DNA damage response and a regulator of DNA double-stranded breaks (DSBs) repair. 53BP1 was recently reported to be a centrosomal protein and a binding partner of mitotic polo-like kinase 1 (Plk1). The stability of 53BP1, in response to DSBs, is regulated by its phosphorylation, deubiquitination, and ubiquitination. During mitosis, 53BP1 is stabilized by phosphorylation at S380, a putative binding region with polo-box domain of Plk1, and deubiquitination by ubiquitin-specific protease 7 (USP7)...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28886438/daidzein-down-regulates-ubiquitin-specific-protease-19-expression-through-estrogen-receptor-%C3%AE-and-increases-skeletal-muscle-mass-in-young-female-mice
#3
Masahiro Ogawa, Takehiro Kitano, Natsuha Kawata, Takashi Sugihira, Tomoya Kitakaze, Naoki Harada, Ryoichi Yamaji
Ubiquitin-specific protease 19 (USP19) is a key player in the negative regulation of muscle mass during muscle atrophy. Loss-of-function approaches demonstrate that 17β-estradiol (E2) increases USP19 expression through estrogen receptor (ER) α and consequently decreases soleus muscle mass in young female mice under physiological conditions. Daidzein is one of the main isoflavones in soy, and activates ERβ-dependent transcription. Here, we investigated the effects of daidzein on E2-increased USP19 expression and E2-decreased soleus muscle mass in young female mice...
August 12, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28881612/the-b-box-module-of-cyld-is-responsible-for-its-intermolecular-interaction-and-cytoplasmic-localization
#4
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881591/usp5-functions-as-an-oncogene-for-stimulating-tumorigenesis-in-hepatocellular-carcinoma
#5
Yi Liu, Wei-Mao Wang, Ying-Fei Lu, Lu Feng, Li Li, Ming-Zhu Pan, Yu Sun, Chun-Wai Suen, Wei Guo, Jian-Xin Pang, Jin-Fang Zhang, Wei-Ming Fu
As deubiquitinases, several ubiquitin specific protease members have been reported to mediate tumorigenesis. Although ubiquitin specific protease 5 (Usp5) was previously demonstrated to suppress p53 transcriptional activity and DNA repair, its role in carcinogenesis remains elusive. In this study, we sought to define a novel role of Usp5 in tumorigenesis. It was found that Usp5 was significantly upregulated in hepatocellular carcinoma (HCC) cells and most clinical specimens. Further functional investigation also showed that Usp5 knockdown suppressed cell proliferation, migration, drug resistance and induced apoptosis; on the other hand, Usp5 overexpression promoted colony formation, migration, drug resistance and tumorigenesis...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881486/how-usp18-deals-with-isg15-modified-proteins-structural-basis-for-the-specificity-of-the-protease
#6
REVIEW
Anja Basters, Klaus-Peter Knobeloch, Günter Fritz
The Ubiquitin-specific protease 18 (USP18) has two major functions: (i) it is a highly specific protease that cleaves the ubiquitin-like modifier ISG15 (interferon stimulated gene 15 kDa) from proteins, and (ii) independent from its enzymatic activity USP18 interacts with the type I interferon receptor and shuts off downstream signaling. The structures of USP18 and a USP18-ISG15 complex revealed the molecular basis of the unique specificity of the protease and might shed some light into its interaction with the interferon receptor...
September 7, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28877990/grb2-mediated-recruitment-of-usp9x-to-lat-enhances-themis-stability-following-thymic-selection
#7
Anne Garreau, Gaëtan Blaize, Jérémy Argenty, Nelly Rouquié, Audrey Tourdès, Stephen A Wood, Abdelhadi Saoudi, Renaud Lesourne
Themis is a new component of the TCR signaling machinery that plays a critical role during T cell development. The positive selection of immature CD4(+)CD8(+) double-positive thymocytes and their commitment to the CD4(+)CD8(-) single-positive stage are impaired in Themis(-/-) mice, suggesting that Themis might be important to sustain TCR signals during these key developmental processes. However, the analysis of Themis mRNA levels revealed that Themis gene expression is rapidly extinguished during positive selection...
September 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28877473/crimean-congo-hemorrhagic-fever-virus-suppresses-innate-immune-responses-via-a-ubiquitin-and-isg15-specific-protease
#8
Florine E M Scholte, Marko Zivcec, John V Dzimianski, Michelle K Deaton, Jessica R Spengler, Stephen R Welch, Stuart T Nichol, Scott D Pegan, Christina F Spiropoulou, Éric Bergeron
Antiviral responses are regulated by conjugation of ubiquitin (Ub) and interferon-stimulated gene 15 (ISG15) to proteins. Certain classes of viruses encode Ub- or ISG15-specific proteases belonging to the ovarian tumor (OTU) superfamily. Their activity is thought to suppress cellular immune responses, but studies demonstrating the function of viral OTU proteases during infection are lacking. Crimean-Congo hemorrhagic fever virus (CCHFV, family Nairoviridae) is a highly pathogenic human virus that encodes an OTU with both deubiquitinase and deISGylase activity as part of the viral RNA polymerase...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28870295/targets-of-ubiquitin-like-system-in-mycobacteria-and-related-actinobacterial-species
#9
REVIEW
Yusuf Akhter, Shweta Thakur
Protein turnover and recycling is a prerequisite in all living organisms to maintain normal cellular physiology. Many bacteria are proteasome deficient but they possess typical protease enzymes for carrying out protein turnover. However, several groups of actinobacteria such as mycobacteria harbor both proteasome and proteases. In these bacteria, for cellular protein turnover the target proteins undergo post-translational modification referred as pupylation in which a small protein Pup (prokaryotic ubiquitin-like protein) is tagged to the specific lysine residues of the target proteins and after that those target proteins undergo proteasomal degradation...
November 2017: Microbiological Research
https://www.readbyqxmd.com/read/28852924/usp10-inhibits-lung-cancer-cell-growth-and-invasion-by-upregulating-pten
#10
Jia Sun, Tianxiang Li, Yinying Zhao, Lirong Huang, Hua Sun, Hui Wu, Xiufeng Jiang
To determine the potential tumor suppressor functions of ubiquitin-specific protease 10 (USP10) in lung cancer and elucidate underlying molecular mechanism. The relative expression of USP10 was determined by real-time PCR and immunoblotting. The inhibitory effect of USP10 on tumor growth was demonstrated on allograft mice with Lewis carcinoma cell inoculation. The relative cell proliferation was measured with Cell Counting Kit-8 (CCK-8). The invasive capacity was evaluated by transwell assay. The interaction between USP10 and Phosphatase And Tensin Homolog (PTEN) was examined by co-immunoprecipitation...
August 29, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28839133/usp26-functions-as-a-negative-regulator-of-cellular-reprogramming-by-stabilising-prc1-complex-components
#11
Bo Ning, Wei Zhao, Chen Qian, Pinghua Liu, Qingtian Li, Wenyuan Li, Rong-Fu Wang
Despite much progress in the comprehension of the complex process of somatic cell reprogramming, many questions regarding the molecular mechanism of regulation remain to be answered. At present, the knowledge on the negative regulation of reprogramming process is indeed poor in contrary to the identification of positive regulators. Here we report for the first time that ubiquitin-specific protease 26 negatively regulates somatic cell-reprogramming process by stabilizing chromobox (CBX)-containing proteins CBX4 and CBX6 of polycomb-repressive complex 1 through the removal of K48-linked polyubiquitination...
August 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28825532/replication-of-a-low-pathogenic-avian-influenza-virus-is-enhanced-by-chicken-ubiquitin-specific-protease-18
#12
Taichiro Tanikawa, Yuko Uchida, Takehiko Saito
Previous research revealed the induction of chicken USP18 (chUSP18) in the lungs of chickens infected with highly pathogenic avian influenza viruses (HPAIVs). This activity was correlated with the degree of pathogenicity of the viruses to chickens. As mammalian ubiquitin-specific protease (USP18) is known to remove type I interferon (IFN I)-inducible ubiquitin-like molecules from conjugated proteins and block IFN I signalling, we explored the function of the chicken homologue of USP18 during avian influenza virus infection...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28817177/the-n-terminal-ubiquitin-associated-domain-of-cezanne-is-crucial-for-its-function-to-suppress-nf-%C3%AE%C2%BAb-pathway
#13
Yanxi Ji, Liu Cao, Lanyi Zeng, Zhen Zhang, Qiaoqiao Xiao, Penglin Guan, Shiyou Chen, Yu Chen, Min Wang, Deyin Guo
Cezanne, a deubiquitinating cysteine protease (DUB) belonging to A20 subgroup of ovarian tumor (OTU) protein superfamily, functions as a negative regulator of NF-κB to attenuate NF-κB activation and to restrain pro-inflammatory transcription in response to TNF receptor (TNFR) signaling. It is the first documented OTU DUB that preferably disassembles Lys11-linked polyubiquitin chains and has been shown to regulate multiple cellular events including immune signaling, cell survival and tumor progression. Previous studies showed that in response to TNF stimulation, Cezanne is recruited to the activated TNFR complex to suppress the build-up of polyubiquitinated RIP1 signal by removing Lys63 polyubiquitin from RIP1...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28807830/usp5-promotes-tumorigenesis-and-progression-of-pancreatic-cancer-by-stabilizing-foxm1-protein
#14
Xin-Yan Li, Hai-Yun Wu, Xiao-Fang Mao, Li-Xin Jiang, Yong-Xiang Wang
Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including glioblastoma, melanoma and hepatocellular carcinoma. However, the role of USP5 in tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) has not been studied yet. In this study, we demonstrated that USP5 was significantly upregulated in a panel of PDAC cell lines and correlated with FoxM1 protein expression. USP5 knockdown inhibited proliferation of PANC-1 and SW1990, two PDAC cell lines. In the mouse xenografted pancreatic tumor model, suppression of USP5 significantly decreased tumor growth, correlated with down regulation of FoxM1...
August 12, 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
#15
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/28805676/inhibitors-of-deubiquitinating-enzymes-block-hiv-1-replication-and-augment-the-presentation-of-gag-derived-mhc-i-epitopes
#16
Christian Setz, Melanie Friedrich, Pia Rauch, Kirsten Fraedrich, Alina Matthaei, Maximilian Traxdorf, Ulrich Schubert
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity...
August 12, 2017: Viruses
https://www.readbyqxmd.com/read/28768102/chemical-approaches-to-intervening-in-ubiquitin-specific-protease-7-usp7-function-for-oncology-and-immune-oncology-therapies
#17
Jian Wu, Suresh Kumar, Feng Wang, Hui Wang, Lijia Chen, Patrick Arsenault, Michael Mattern, Joseph Weinstock
USP7, the most widely studied among the nearly 100 deubiquitinating enzymes, supports cancer by positively affecting tumor growth and negatively affecting the patient's immune response to tumors. Great interest exists, therefore, in developing USP7 inhibitors for clinical evaluation. While the proteasome inhibitor field has enjoyed clinical success, very few clinically appropriate effectors of deubiquitinating (protease) or ubiquitinating (ligase) enzymes have appeared. The ubiquitin protease/ligase field is moving from the initial discovery of potent, selective modulators with cell proof of concept and/or in vivo activity to the optimization of these molecules to impart drug-like properties or the discovery of new inhibitor scaffolds by improved screening or rational design...
August 2, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28755289/downregulation-of-usp4-promotes-activation-of-microglia-and-subsequent-neuronal-inflammation-in-rat-spinal-cord-after-injury
#18
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/28743957/ubiquitin-specific-protease-21-stabilizes-brca2-to-control-dna-repair-and-tumor-growth
#19
Jinping Liu, Alex Kruswick, Hien Dang, Andy D Tran, So Mee Kwon, Xin Wei Wang, Philipp Oberdoerffer
Tumor growth relies on efficient DNA repair to mitigate the detrimental impact of DNA damage associated with excessive cell division. Modulating repair factor function, thus, provides a promising strategy to manipulate malignant growth. Here, we identify the ubiquitin-specific protease USP21 as a positive regulator of BRCA2, a key mediator of DNA repair by homologous recombination. USP21 interacts with, deubiquitinates and stabilizes BRCA2 to promote efficient RAD51 loading at DNA double-strand breaks. As a result, depletion of USP21 decreases homologous recombination efficiency, causes an increase in DNA damage load and impairs tumor cell survival...
July 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28718215/usp18-protects-against-hepatic-steatosis-and-insulin-resistance-via-its-dub-activity
#20
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
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