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Ubiquitin-specific protease

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https://www.readbyqxmd.com/read/28302046/the-role-of-the-complex-usp1-wdr48-in-differentiation-and-proliferation-processes-in-cancer-stem-cells
#1
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
#2
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
#3
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...
March 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28284030/sumo-conjugation-a-mechanistic-view
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28250277/molecular-dynamic-studies-of-interferon-and-innate-immunity-resistance-in-mers-cov-non-structural-protein-3
#7
Manal Alfuwaires, Abdallah Altaher, Mahmoud Kandeel
The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate MERS CoV Non-Structural Protein 3 (NSP3) specific proteins that resist host innate immunity. MERS CoV papain-like protease (Plpro) was more conformationally flexible than Severe Acute Respiratory Syndrome CoV (SARS) CoV Plpro...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28245560/the-regulations-of-deubiquitinase-usp15-and-its-pathophysiological-mechanisms-in-diseases
#8
REVIEW
Chon-Kit Chou, Yu-Ting Chang, Michal Korinek, Yei-Tsung Chen, Ya-Ting Yang, Steve Leu, I-Ling Lin, Chin-Ju Tang, Chien-Chih Chiu
Deubiquitinases (DUBs) play a critical role in ubiquitin-directed signaling by catalytically removing the ubiquitin from substrate proteins. Ubiquitin-specific protease 15 (USP15), a member of the largest subfamily of cysteine protease DUBs, contains two conservative cysteine (Cys) and histidine (His) boxes. USP15 harbors two zinc-binding motifs that are essential for recognition of poly-ubiquitin chains. USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific proteases (DUSP) domain and ubiquitin-like (UBL) domain...
February 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28223825/usp21-promotes-cell-proliferation-and-metastasis-through-suppressing-ezh2-ubiquitination-in-bladder-carcinoma
#9
Yong Chen, Bo Zhou, Daihui Chen
Bladder cancer (BC) is the second most common malignant tumor of the urinary tract in the world. In this study, we found that ubiquitin-specific protease (USP21) was upregulated in BC and the ectopic expression of USP21 was closely associated with tumor size and metastasis. Moreover, patients with higher levels of USP21 had poorer survival rate. Multiple function analysis such as CCK-8, colony formation, wound healing, and transwell analysis indicated that USP21 regulated cell proliferation and metastasis in bladder carcinoma cell lines...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#10
Tao An, Yaxiao Gong, Xue Li, Lingmei Kong, Pengcheng Ma, Liang Gong, Huifang Zhu, Chunlei Yu, Jianmei Liu, Hongyu Zhou, Bingyu Mao, Yan Li
Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28196907/acetylation-dependent-regulation-of-mdm2-e3-ligase-activity-dictates-its-oncogenic-function
#11
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/28187457/the-b-box-module-of-cyld-is-responsible-for-its-intermolecular-interaction-and-cytoplasmic-localization
#12
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/28167606/the-deubiquitinating-enzyme-usp20-regulates-erk3-stability-and-biological-activity
#13
Simon Mathien, Paul Déléris, Mathilde Soulez, Laure Voisin, Sylvain Meloche
Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein (MAP) kinase whose regulatory mechanisms and biological functions remain superficially understood. Contrary to most protein kinases, ERK3 is a highly unstable protein that is subject to dynamic regulation by the ubiquitin-proteasome system. However, the effectors that control ERK3 ubiquitination and degradation are unknown. In this study, we carried out an unbiased functional loss-of-function screen of the human deubiquitinating enzyme (DUB) family and identified ubiquitin-specific protease 20 (USP20) as a novel ERK3 regulator...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28165509/structural-basis-of-the-specificity-of-usp18-toward-isg15
#14
Anja Basters, Paul P Geurink, Annika Röcker, Katharina F Witting, Roya Tadayon, Sandra Hess, Marta S Semrau, Paola Storici, Huib Ovaa, Klaus-Peter Knobeloch, Günter Fritz
Protein modification by ubiquitin and ubiquitin-like modifiers (Ubls) is counteracted by ubiquitin proteases and Ubl proteases, collectively termed DUBs. In contrast to other proteases of the ubiquitin-specific protease (USP) family, USP18 shows no reactivity toward ubiquitin but specifically deconjugates the interferon-induced Ubl ISG15. To identify the molecular determinants of this specificity, we solved the crystal structures of mouse USP18 alone and in complex with mouse ISG15. USP18 was crystallized in an open and a closed conformation, thus revealing high flexibility of the enzyme...
February 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28160502/deubiquitinating-enzyme-usp22-positively-regulates-c-myc-stability-and-tumorigenic-activity-in-mammalian-and-breast-cancer-cells
#15
Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28151478/proteasome-associated-deubiquitinase-ubiquitin-specific-protease-14-regulates-prostate-cancer-proliferation-by-deubiquitinating-and-stabilizing-androgen-receptor
#16
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/28148530/usp40-gene-knockdown-disrupts-glomerular-permeability-in-zebrafish
#17
Hisashi Takagi, Yukino Nishibori, Kan Katayama, Tomohisa Katada, Shohei Takahashi, Zentaro Kiuchi, Shin-Ichiro Takahashi, Hiroyasu Kamei, Hayato Kawakami, Yoshihiro Akimoto, Akihiko Kudo, Katsuhiko Asanuma, Hiromu Takematsu, Kunimasa Yan
Unbiased transcriptome profiling and functional genomics approaches have identified ubiquitin specific protease 40 (USP40) as a highly specific glomerular transcript. This gene product remains uncharacterized, and its biological function is completely unknown. Here, we showed that mouse and rat glomeruli exhibit specific expression of the USP40 protein, which migrated at 150 kDa and was exclusively localized in the podocyte cytoplasm of the adult kidney. Double-labeling immunofluorescence staining and confocal microscopy analysis of fetal and neonate kidney samples revealed that USP40 was also expressed in the vasculature, including in glomerular endothelial cells at the premature stage...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28137592/usp7-promotes-medulloblastoma-cell-survival-and-metastasis-by-activating-shh-pathway
#18
Meixiao Zhan, Xiaohan Sun, Jinxiao Liu, Yan Li, Yong Li, Xu He, Zizhang Zhou, Ligong Lu
The ubiquitin-specific protease Usp7 plays roles in multiple cellular processes through deubiquitinating and stabilizing numerous substrates, including P53, Pten and Gli. Aberrant Usp7 activity has been implicated in many disorders and tumorigenesis, making it as a potential target for therapeutic intervention. Although it is clear that Usp7 is involved in many types of cancer, its role in regulating medulloblastoma (MB) is still unknown. In this study, we show that knockdown of Usp7 inhibits the proliferation and migration of MB cells, while Usp7 overexpression exerts an opposite effect...
January 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28126338/usp15-attenuates-igf-i-signaling-by-antagonizing-nedd4-induced-irs-2-ubiquitination
#19
Toshiaki Fukushima, Hidehito Yoshihara, Haruka Furuta, Fumihiko Hakuno, Shun-Ichiro Iemura, Tohru Natsume, Yusuke Nakatsu, Hideaki Kamata, Tomoichiro Asano, Masayuki Komada, Shin-Ichiro Takahashi
Insulin receptor substrates (IRSs) are phosphorylated by IGF-I receptor tyrosine kinase in a ligand-dependent manner. In turn, they bind to and activate effector proteins such as PI3K, leading to various cell responses including cell proliferation. We had reported that ubiquitin ligase Nedd4 induces mono-ubiquitination of IRS-2, thereby enhancing IRS-2 tyrosine phosphorylation, leading to increased IGF signaling and mitogenic activity. Here we show that ubiquitin-specific protease 15 (USP15) antagonizes the effect of Nedd4 on IRS-2...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28108249/synthesis-and-biological-evaluation-of-thiazole-derivatives-as-novel-usp7-inhibitors
#20
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
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