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Ubiquitin-specific protease

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https://www.readbyqxmd.com/read/28431405/usp5-functions-as-an-oncogene-for-stimulating-tumorigenesis-in-hepatocellular-carcinoma
#1
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...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417919/sumo-specific-cysteine-protease-1-promotes-epithelial-mesenchymal-transition-of-prostate-cancer-cells-via-regulating-smad4-desumoylation
#2
Xiaoyan Zhang, Hao Wang, Hua Wang, Fengjun Xiao, Prem Seth, Weidong Xu, Qinghua Jia, Chutse Wu, Yuefeng Yang, Lisheng Wang
In advanced prostate cancer, small ubiquitin-like modifier (SUMO)-specific cysteine protease 1 (SENP1) is up-regulated. However, the role of SENP1 in regulating deSUMOylation of TGF-β/SMADs signaling is unknown. In this study, we developed a lentiviral vector, PLKO.1-shSENP1, to silence SENP1 in prostate cancer cells with high metastatic characteristics (PC3M). Likewise, we also created an adenovirus vector, Ad5/F11p-SENP1 to over-express SENP1 in prostate cancer cells with low metastatic potential (LNCaP)...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28417539/usp22-mediates-the-multidrug-resistance-of-hepatocellular-carcinoma-via-the-sirt1-akt-mrp1-signaling-pathway
#3
Sunbin Ling, Jie Li, Qiaonan Shan, Haojiang Dai, Di Lu, Xue Wen, Penghong Song, Haiyang Xie, Lin Zhou, Jimin Liu, Xiao Xu, Shusen Zheng
Drug treatments for hepatocellular carcinoma (HCC) often fail because of multidrug resistance (MDR). The mechanisms of MDR are complex but cancer stem cells (CSC), which are able to self-renew and differentiate, have recently been shown to be involved. The deubiquitinating enzyme ubiquitin-specific protease 22 (USP22) is a marker for CSCs. This study aimed to elucidate the role of USP22 in MDR of HCC and the underlying mechanisms. Using in vitro and in vivo assays, we found that modified USP22 levels were responsible for the altered drug-resistant phenotype of BEL7402 and BEL/FU cells...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28415623/overexpression-of-ubiquitin-specific-proteases-44-promotes-the-malignancy-of-glioma-by-stabilizing-tumor-promoter-securin
#4
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...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415621/usp22-maintains-gastric-cancer-stem-cell-stemness-and-promotes-gastric-cancer-progression-by-stabilizing-bmi1-protein
#5
Yue Ma, Hua-Lin Fu, Zhen Wang, Hai Huang, Jian Ni, Jie Song, Ying Xia, Wei-Lin Jin, Da-Xiang Cui
Increased ubiquitin-specific protease 22 (USP22) has been associated with poor prognosis in several cancers including gastric cancer. However, the role of USP22 in gastric tumorigenesis is still unclear. Gastric cancer stem cells have been identified and shown to correlate with gastric cancer initiation and metastasis. In this study, we found that silencing of USP22 inhibited proliferation of gastric cancer cells and suppressed the cancer stem cell spheroid formation in serum-free culture. Furthermore, cancer stem cell markers, such as CD133, SOX2, OCT4 and NANOG were down-regulated...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414040/sars-coronavirus-papain-like-protease-up-regulates-the-collagen-expression-through-non-samd-tgf-%C3%AE-1-signaling
#6
Ching-Ying Wang, Chien-Yi Lu, Shih-Wen Li, Chien-Chen Lai, Chun-Hung Hua, Su-Hua Huang, Ying-Ju Lin, Mann-Jen Hour, Cheng-Wen Lin
SARS coronavirus (CoV) papain-like protease (PLpro) reportedly induced the production of TGF-β1 through p38 MAPK/STAT3-meidated Egr-1-dependent activation (Sci. Rep. 6, 25754). This study investigated the correlation of PLpro-induced TGF-β1 with the expression of Type I collagen in human lung epithelial cells and mouse pulmonary tissues. Specific inhibitors for TGF-βRI, p38 MAPK, MEK, and STAT3 proved that SARS-CoV PLpro induced TGF-β1-dependent up-regulation of Type I collagen in vitro and in vivo. Subcellular localization analysis of SMAD3 and SMAD7 indicated that non-SMAD pathways in TGF-β1 signaling involved in the production of Type I collagen in transfected cells with pSARS-PLpro...
April 13, 2017: Virus Research
https://www.readbyqxmd.com/read/28391724/usp19-suppresses-cellular-type-i-interferon-signaling-by-targeting-traf3-for-deubiquitination
#7
Zhiwen Gu, Weifeng Shi, Li Zhang, Zhilin Hu, Chao Xu
AIM: To investigate host factors that mediate the immune escape of enterovirus 71 (EV71) in the context of deubiquitinating enzymes. MATERIALS & METHODS: Utilize PCR array to screen candidate genes that may be involved in EV71-induced cellular antiviral immune responses, and utilize protein mass spectrometry analysis to identify the functional targets of the candidate regulator. RESULTS: EV71 infection induces the upregulation of ubiquitin-specific protease 19 (USP19) gene expression, which negatively regulates cellular antiviral type I interferon signaling...
April 10, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28385661/intact-cell-maldi-tof-mass-spectrometry-on-single-bovine-oocyte-and-follicular-cells-combined-with-top-down-proteomics-a-novel-approach-to-characterise-markers-of-oocyte-maturation
#8
Valérie Labas, Ana-Paula Teixeira-Gomes, Laura Bouguereau, Audrey Gargaros, Lucie Spina, Aurélie Marestaing, Svetlana Uzbekova
Intact cell MALDI-TOF mass spectrometry (ICM-MS) was adapted to bovine follicular cells from individual ovarian follicles to obtain the protein/peptide signatures (<17kDa) of single oocytes, cumulus cells (CC) and granulosa cells (GC), which shared a total of 439 peaks. By comparing the ICM-MS profiles of single oocytes with CC before and after in vitro maturation (IVM), 71 different peaks were characterised, and their relative abundance was found to vary depending on the stage of oocyte meiotic maturation...
April 3, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28369997/gene-expression-profile-after-knockdown-of-usp18-in-hepg2-2-15-cells
#9
Lin Li, Qing-Song Lei, Ling-Na Kong, Shu-Jun Zhang, Bo Qin
In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2...
March 31, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28364380/ubiquitin-specific-protease-14-regulates-lps-induced-inflammation-by-increasing-erk1-2-phosphorylation-and-nf-%C3%AE%C2%BAb-activation
#10
Ningning Liu, Tianyu Kong, Xiaohua Chen, Huan Hu, Hongjiao Gu, Shiming Liu, Xiaohui Chen, Qilin Yang, Aiqun Li, Xuming Xiong, Zhenhui Zhang
Persistent activation of nuclear factor B (NF-κB) is very important in the modulation of macrophages cellular response to microbial infections. The deubiquitinase USP14, which is critical for ubiquitin-mediated proteasomal degradation of proteins, is known to be involved in cancer, neurological diseases, and aging. However, the mechanism by which USP14 regulates inflammation remains unclear. Here, we demonstrated that decreasing the deubiquitinase activity of USP14 resulted in reduced lipopolysaccharides (LPS)-mediated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 release in THP-1 and RAW264...
March 31, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28351334/upregulation-of-senp3-smt3ip1-promotes-epithelial-ovarian-cancer-progression-and-forecasts-poor-prognosis
#11
Jialin Cheng, Min Su, Yunfeng Jin, Qinghua Xi, Yan Deng, Jie Chen, Wei Wang, Yannan Chen, Lingling Chen, Nannan Shi, Guoxin Mao
As a crucial member of the small ubiquitin-like modifier system, SUMO-specific protease 3, was identified to be essential for cell proliferation and ribosomal RNA processing. Recent studies showed that SUMO-specific protease 3 was elevated in ovarian cancer compared to normal tissue samples. However, the connection between SUMO-specific protease 3-specific expression and clinicopathological parameters of epithelial ovarian cancer, as well as the physiologically potential role of SUMO-specific protease 3 in epithelial ovarian cancer remained unclear...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28336234/ubiquitin-specific-protease-4-usp4-suppresses-myoblast-differentiation-by-down-regulating-myod-activity-in-a-catalytic-independent-manner
#12
Sun-Il Yun, Kyeong Kyu Kim
For myotube formation, proliferation and differentiation of myoblasts must be tightly regulated by various myogenic regulatory factors (MRFs) such as MyoD, myogenic factor 5 (Myf5), myogenin, and muscle-specific regulatory factor 4 (MRF4). However, it is not clear how the expression or activity of these MRFs is controlled during myogenesis. In this study, we identified ubiquitin-specific protease 4 (USP4), one of deubiquitinating enzymes, as a suppressor of MRFs by demonstrating that a knockdown of USP4 enhances myogenesis by controlling MyoD and the level of myogenesis marker proteins in C2C12 cells...
March 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28327663/tandem-uims-confer-lys48-ubiquitin-chain-substrate-preference-to-deubiquitinase-usp25
#13
Kohei Kawaguchi, Kazune Uo, Toshiaki Tanaka, Masayuki Komada
Ubiquitin-specific protease (USP) 25, belonging to the USP family of deubiquitinases, harbors two tandem ubiquitin-interacting motifs (UIMs), a ~20-amino-acid α-helical stretch that binds to ubiquitin. However, the role of the UIMs in USP25 remains unclear. Here we show that the tandem UIM region binds to Lys48-, but not Lys63-, linked ubiquitin chains, where the two UIMs played a critical and cooperative role. Purified USP25 exhibited higher ubiquitin isopeptidase activity to Lys48-, than to Lys63-, linked ubiquitin chains...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325877/dual-utility-nls-drives-rnf169-dependent-dna-damage-responses
#14
Liwei An, Yiyang Jiang, Howin H W Ng, Ellen P S Man, Jie Chen, Ui-Soon Khoo, Qingguo Gong, Michael S Y Huen
Loading of p53-binding protein 1 (53BP1) and receptor-associated protein 80 (RAP80) at DNA double-strand breaks (DSBs) drives cell cycle checkpoint activation but is counterproductive to high-fidelity DNA repair. ring finger protein 169 (RNF169) maintains the balance by limiting the deposition of DNA damage mediator proteins at the damaged chromatin. We report here that this attribute is accomplished, in part, by a predicted nuclear localization signal (NLS) that not only shuttles RNF169 into the nucleus but also promotes its stability by mediating a direct interaction with the ubiquitin-specific protease USP7...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28302046/the-role-of-the-complex-usp1-wdr48-in-differentiation-and-proliferation-processes-in-cancer-stem-cells
#15
Jussara Maria Gonçalves, Mabel Mariela Rodriguez Cordeiro, Elena Riet Correa Rivero
Recently some studies identified the Basic-Helix-Loop-Helix (bHLH) transcription factor as a significant regulator for the evolution of neoplasms. The binding between bHLH proteins and DNA is restricted by heterodimerization with Inhibitors of DNA binding (ID). IDs prevent cellular differentiation, promote growth and sustain tumor development. The wide presence of stem cells in cancers suggests that genes ID are essential to cancer stem cells (CSC) progress. The enzyme Ubiquitin-specific protease 1 (USP1) is reported by deubiquitination and stabilization of IDs...
March 15, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28301771/recognition-of-client-proteins-by-the-proteasome
#16
Houqing Yu, Andreas Matouschek
The ubiquitin proteasome system controls the concentrations of regulatory proteins and removes damaged and misfolded proteins from cells. Proteins are targeted to the protease at the center of this system, the proteasome, by ubiquitin tags, but ubiquitin is also used as a signal in other cellular processes. Specificity is conferred by the size and structure of the ubiquitin tags, which are recognized by receptors associated with the different cellular processes. However, the ubiquitin code remains ambiguous, and the same ubiquitin tag can target different proteins to different fates...
March 9, 2017: Annual Review of Biophysics
https://www.readbyqxmd.com/read/28286270/usp39-a-direct-target-of-microrna-133a-promotes-progression-of-pancreatic-cancer-via-the-akt-pathway
#17
Jing Cai, Tiande Liu, Peng Huang, Wei Yan, Changkuo Guo, Le Xiong, Anwen Liu
Ubiquitin specific protease 39 (USP39) is one of the deubiquitinating enzymes without ubiquitin protease activity, which has been implicated in the progression of several cancers. However, the role of USP39 in pancreatic cancer (PC) is largely unknown. In present study, we found that USP39 expression was elevated in PC tissues than adjacent non-tumor tissues. Importantly, we demonstrated that overexpression of USP39 is closely correlated with tumor progression and poor survival in PC patients. Furthermore, high USP39 expression was observed in PC cell lines and ectopic expression of USP39 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas silencing USP39 suppressed growth of PC cells...
April 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28284030/sumo-conjugation-a-mechanistic-view
#18
REVIEW
Andrea Pichler, Chronis Fatouros, Heekyoung Lee, Nathalie Eisenhardt
The regulation of protein fate by modification with the small ubiquitin-related modifier (SUMO) plays an essential and crucial role in most cellular pathways. Sumoylation is highly dynamic due to the opposing activities of SUMO conjugation and SUMO deconjugation. SUMO conjugation is performed by the hierarchical action of E1, E2 and E3 enzymes, while its deconjugation involves SUMO-specific proteases. In this review, we summarize and compare the mechanistic principles of how SUMO gets conjugated to its substrate...
March 1, 2017: Biomolecular Concepts
https://www.readbyqxmd.com/read/28267608/analysis-of-the-mirna-profile-in-c6-36-cells-persistently-infected-with-dengue-virus-type-2
#19
Rodolfo Gamaliel Avila-Bonilla, Martha Yocupicio-Monroy, Laurence A Marchat, Mónica A De Nova-Ocampo, Rosa María Del Ángel, Juan Santiago Salas-Benito
Dengue virus (DENV) is the most important arbovirus in the world; DENV is transmitted by the Aedes genus of mosquitoes and can establish a life-long persistent infection in mosquitoes. However, the exact mechanism by which persistent infection is established remains unknown. In this study the differential expression of miRNAs was analysed by deep sequencing and RT-qPCR using a previously established C6/36-HT cell line persistently infected with DENV 2 (C6-L) as a model. miR-927, miR-87, miR-210, miR-2a-3p, miR-190 and miR-970 were up-regulated, whereas miR-252, miR-263a-3p, miR-92b, miR-10-5p miR-9a-5p, miR-9a-1, miR-124, miR-286a and miR-286b were down-regulated in C6-L cells compared with C6/36 cells acutely infected with the same virus or mock-infected cells...
March 4, 2017: Virus Research
https://www.readbyqxmd.com/read/28258134/senp1-promotes-hypoxia-induced-cancer-stemness-by-hif-1%C3%AE-desumoylation-and-senp1-hif-1%C3%AE-positive-feedback-loop
#20
Chun-Ping Cui, Carmen Chak-Lui Wong, Alan Ka-Lun Kai, Daniel Wai-Hung Ho, Eunice Yuen-Ting Lau, Yu-Man Tsui, Lo-Kong Chan, Tan-To Cheung, Kenneth Siu-Ho Chok, Albert C Y Chan, Regina Cheuk-Lam Lo, Joyce Man-Fong Lee, Terence Kin-Wah Lee, Irene Oi Lin Ng
OBJECTIVE: We investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness. DESIGN: HCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs...
March 3, 2017: Gut
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