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Le Yu, Ling Dong, Yang Wang, Liu Liu, Hua Long, Hui Li, Jinping Li, Xiaolong Yang, Zhaojian Liu, Guangjie Duan, Xiaotian Dai, Zhenghong Lin
Upregulation of special AT-rich sequence-binding protein-1 (SATB1) has been suggested to promote tumor growth and metastasis. However, the factors governing its cellular levels remain unclear. Here, we report that ubiquitin-specific peptidase 47 (USP47), a member of the deubiquitinating enzymes family, interacts with SATB1 and mediates its deubiquitination and stability. USP47 deficiency impairs transcriptional activity of SATB1 target genes and inhibits colon cancer cell proliferation, migration, and tumorigenesis in a mouse model of colon cancer...
February 8, 2019: Cancer Letters
Tsui-Ling Chang, Pei-Shin Liou, Pei-Yuan Cheng, Hsiang-Ning Chang, Pei-Jane Tsai
Targeting the two degradation systems, ubiquitin proteasome pathway and ubiquitin signal autophagy lysosome system, plays an important function in cancer prevention. Borneol is called an "upper guiding drug". Luteolin has demonstrated anticancer activity. The fact that borneol regulates luteolin can be sufficient to serve as an alternative strategy. Borneol activates luteolin to inhibit E1 and 20S activity (IC50 = 118.8 ± 15.7 μM) and perturb the 26S proteasome structure in vitro. Borneol regulates luteolin to inhibit 26S activity (IC50 = 157 ± 19 μM), induces apoptosis (LC50 = 134 ± 4 μM), and causes pre-G1 and G0/G1 arrest in HepG2 cells...
August 8, 2018: Journal of Agricultural and Food Chemistry
Lara Naghavi, Martin Schwalbe, Ahmed Ghanem, Michael Naumann
Every year, gastric cancer causes around 819,000 deaths worldwide. The incidence of gastric cancer in the western world is slowly declining, but the prognosis is unpromising. In Germany, the 5-year-survival rate is around 32%, and the average life span after diagnosis is 6 to 9 months. Therapy of gastric cancer patients comprises a gastrectomy and perioperative or adjuvant chemotherapy. However, resistance of gastric cancer cells to these agents is widespread; thus, improved chemotherapeutic approaches are required...
May 22, 2018: Biomedicines
Bae-Jung Choi, Sin-Aye Park, Sung-Young Lee, Young Nam Cha, Young-Joon Surh
During the metastatic phase, cancer cells require the dissolution of cadherin-mediated cell-cell adhesion and a dramatic re-organization of the cytoskeleton through epithelial-mesenchymal transition (EMT), thereby acquiring migratory and invasive capabilities. In most tumors, EMT is accompanied by hypoxia. However, the intracellular signaling molecule that mediates hypoxia-induced EMT remained overlooked. By utilizing the microarray database system of the Cancer Genome Atlas, we identified ubiquitin-specific protease 47 (USP47), a deubiquitinating enzyme, as a potential mediator of hypoxia-induced EMT...
November 21, 2017: Scientific Reports
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
Dariel Ashton-Beaucage, Caroline Lemieux, Christian M Udell, Malha Sahmi, Samuel Rochette, Marc Therrien
RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus. Disruption of this pathway is widely observed in cancer and other pathologies. Consequently, considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation. While much information has been garnered on the steps leading up to the activation and inactivation of core pathway components, comparatively little is known on the mechanisms controlling their expression and turnover...
August 2016: PLoS Biology
Jiandang Shi, Yajuan Liu, Xuehe Xu, Wen Zhang, Tianxin Yu, Jianhang Jia, Chunming Liu
Wnt signaling plays important roles in development and tumorigenesis. A central question about the Wnt pathway is the regulation of β-catenin. Phosphorylation of β-catenin by CK1α and GSK3 promotes β-catenin binding to β-TrCP, leading to β-catenin degradation through the proteasome. The phosphorylation and ubiquitination of β-catenin have been well characterized; however, it is unknown whether and how a deubiquitinase is involved. In this study, by screening RNA interference (RNAi) libraries, we identified USP47 as a deubiquitinase that prevents β-catenin ubiquitination...
October 2015: Molecular and Cellular Biology
Jinhua Piao, Aika Tashiro, Minako Nishikawa, Yutaka Aoki, Eiko Moriyoshi, Akira Hattori, Hideaki Kakeya
In this study, the physicochemical and enzymatic properties of recombinant human ubiquitin (Ub)-specific protease (USP) 47, a novel member of the C19 family of de-ubiquitinating enzymes (DUB), were characterized for the first time. Recombinant human USP47 was expressed in a baculovirus expression system and purified to homogeneity. The purified protein was shown to be a monomeric protein with a molecular mass of ∼146 kDa on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. USP47 released Ub from Ub-aminoacyl-4-metheylcoumaryl-7-amide and Ub-tagged granzyme B...
December 2015: Journal of Biochemistry
Binbin Zhang, Yuan Yin, Yaling Hu, Jiwei Zhang, Zehua Bian, Mingxu Song, Dong Hua, Zhaohui Huang
MicroRNAs (miRNAs) are a type of small noncoding RNAs that are strongly implicated in carcinogenesis. However, the potential diagnostic, prognostic and therapeutic roles of the majority of miRNAs in the pathological processes of tumorigenesis remain largely unknown. Our and others' data revealed that miR-204-5p was significantly downregulated in gastrointestinal tumor tissues compared with adjacent noncancerous tissues. The downregulation of miR-204-5p was confirmed in our gastric cancer (GC) cohort, and we showed that ectopic expression of miR-204-5p inhibited, whereas silencing miR-204-5p expression promoted GC cell proliferation in vitro...
January 2015: Medical Oncology
Kyoko Sako-Kubota, Nobutoshi Tanaka, Shigenori Nagae, Wenxiang Meng, Masatoshi Takeichi
The adherens junction (AJ) plays a crucial role in maintaining cell-cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end-directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs...
December 1, 2014: Molecular Biology of the Cell
Catherine M Nickson, Jason L Parsons
Base excision repair (BER) is the predominant cellular mechanism by which human cells repair DNA base damage, sites of base loss, and DNA single strand breaks of various complexity, that are generated in their thousands in every human cell per day as a consequence of cellular metabolism and exogenous agents, including ionizing radiation. Over the last three decades the comet assay has been employed in scientific research to examine the cellular response to these types of DNA damage in cultured cells, therefore revealing the efficiency and capacity of BER...
2014: Frontiers in Genetics
Joseph Weinstock, Jian Wu, Ping Cao, William D Kingsbury, Jeffrey L McDermott, Matthew P Kodrasov, Devin M McKelvey, K G Suresh Kumar, Seth J Goldenberg, Michael R Mattern, Benjamin Nicholson
Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to decrease DNA polymerase β (Polβ), both of which are potential anticancer effects. A new class of dual small molecule inhibitors of these enzymes has been discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines...
October 11, 2012: ACS Medicinal Chemistry Letters
Tsui-Ling Chang, Shu-Wei Lin, Shuo-lun Wu, Chu-Mei Hong
Little attention has been devoted to studying the roles of natural antioxidants in the ubiquitin-proteasome pathway during oxidative stress. We demonstrated that a time course revealed that the reassociation of the 19S regulators with the 20S proteasomes occurred automatically and rapidly to reconstitute the 26S proteasomes, with up to 80% completion, within 5 min after H2O2 treatment. Ubiquitin, methyl gallate and tannic acid are able to prevent H2O2 from inhibiting the 26S activity. We further show that the level of the ubiquitin, S5a and 20S core subunits decreased within 30 min and increased after 24 h of H2O2 treatment in Hep-2 cells...
November 2013: Journal of Nutritional Biochemistry
A T Tran, M N Rahim, C Ranadheera, A Kroeker, J P Cortens, K J Opanubi, J A Wilkins, K M Coombs
Cell death is a characteristic consequence of cellular infection by influenza virus. Mounting evidence indicates the critical involvement of host-mediated cellular death pathways in promoting efficient influenza virus replication. Furthermore, it appears that many signaling pathways, such as NF-κB, formerly suspected to solely promote cell survival, can also be manipulated to induce cell death. Current understanding of the cell death pathways involved in influenza virus-mediated cytopathology and in virus replication is limited...
2013: Cell Death & Disease
Seung Wook Yang, Kyu Hee Oh, Esther Park, Hyun Min Chang, Jung Mi Park, Min Woo Seong, Seung Hyeun Ka, Woo Keun Song, Dong Eun Park, Peter W Baas, Young Joo Jeon, Chin Ha Chung
Katanin is a heterodimeric enzyme that severs and disassembles microtubules. While the p60 subunit has the enzyme activity, the p80 subunit regulates the p60 activity. The microtubule-severing activity of katanin plays an essential role in axonal growth. However, the mechanisms by which neuronal cells regulate the expression of katanin-p60 remains unknown. Here we showed that USP47 and C terminus of Hsp70-interacting protein (CHIP) antagonistically regulate the stability of katanin-p60 and thereby axonal growth...
July 31, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jason L Parsons, Irina I Dianova, Svetlana V Khoronenkova, Mariola J Edelmann, Benedikt M Kessler, Grigory L Dianov
DNA base excision repair (BER) is an essential cellular process required for genome stability, and misregulation of BER is linked to premature aging, increased rate of mutagenesis, and cancer. We have now identified the cytoplasmic ubiquitin-specific protease USP47 as the major enzyme involved in deubiquitylation of the key BER DNA polymerase (Pol β) and demonstrate that USP47 is required for stability of newly synthesized cytoplasmic Pol β that is used as a source for nuclear Pol β involved in DNA repair...
March 4, 2011: Molecular Cell
A Peschiaroli, J R Skaar, M Pagano, G Melino
Ubiquitin-specific proteases (USPs) are a subclass of cysteine proteases that catalyze the removal of ubiquitin (either monomeric or chains) from substrates, thus counteracting the activity of E3 ubiquitin ligases. Although the importance of USPs in a multitude of processes, from hereditary cancer to neurodegeneration, is well established, our knowledge on their mode of regulation, substrate specificity and biological function is quite limited. In this study we identify USP47 as a novel interactor of the E3 ubiquitin ligase, Skp1/Cul1/F-box protein beta-transducin repeat-containing protein (SCF(beta-Trcp))...
March 4, 2010: Oncogene
Richard Buus, Monica Faronato, Dean E Hammond, Sylvie Urbé, Michael J Clague
The scattering response of epithelial cells to activation of the Met receptor tyrosine kinase represents one facet of an "invasive growth" program. It is a complex event that incorporates loss of cell-cell adhesion, morphological changes, and cell motility. Ubiquitination is a reversible posttranslational modification that may target proteins for degradation or coordinate signal transduction pathways. There are approximately 79 active deubiquitinating enzymes (DUBs) predicted in the human genome. Here, via a small interfering RNA (siRNA) library approach, we have identified 12 DUBs that are necessary for aspects of the hepatocyte growth factor (HGF)-dependent scattering response of A549 cells...
September 15, 2009: Current Biology: CB
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