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Qiong Chen, Yuanyuan Hang, Tingting Zhang, Li Tan, Shuangdi Li, Yuli Jin
Endometriosis has been initially described as endometrial-like tissue outside of the uterine cavity. Mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) signaling pathway playing an important role in the regulation of cell proliferation, apoptosis and migration has been found to be activated in endometriosis. However, the regulation of MEK/ERK signaling pathway in endometriosis has not been fully understood. In this study, primary-cultured endometrial stromal cells were collected from patients with endometriosis and healthy controls, and the proliferation, apoptosis and migration of ectopic endometrial stromal cells transfected with ubiquitin-specific protease 10 (USP10)-siRNA or pLVX-Puro-USP10 with or without MEK inhibitor PD98059 or exogenous signaling stimulation such as epidermal growth factor (EGF) were measured by CCK-8, flow cytometry and Transwell, respectively...
October 3, 2018: American Journal of Physiology. Cell Physiology
Kozo Nagai, Lihong Hou, Li Li, Bao Nguyen, Tessa Seale, Courtney Shirley, Hayley Ma, Mark Levis, Gabriel Ghiaur, Amy Duffield, Donald Small
Acute myeloid leukemia (AML) patients with FLT3/ITD mutations have a poor prognosis. Monotherapy with selective FLT3 tyrosine kinase inhibitors (TKIs) have shown transient and limited efficacy due to the development of resistance. Arsenic trioxide (ATO, As2 O3 ) has been proven effective in treating acute promyelocytic leukemia (APL) and has shown activity in some cases of refractory and relapsed AML and other hematologic malignances. We explored the feasibility of combining FLT3 TKIs with ATO in the treatment of FLT3/ITD+ leukemias...
August 31, 2018: Oncotarget
Elena Zerkalenkova, Svetlana Lebedeva, Anna Kazakova, Pavel Baryshev, Claus Meyer, Rolf Marschalek, Galina Novichkova, Michael Maschan, Aleksey Maschan, Yulia Olshanskaya
We present a leukemia case that exhibits a chromosomal translocation t(11;16)(q23;q23), which results in the expression of a novel KMT2A fusion gene. This novel fusion, KMT2A-USP10, was found in a relapse of acute myeloid leukaemia M5a. USP10 belongs to a protein family that deubiquitinates a distinct set of target proteins, and thus, increases the steady state protein levels of its target subproteome. One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event...
October 2018: Genes, Chromosomes & Cancer
Javier Rodriguez, Ana Herrero, Shuijie Li, Nora Rauch, Andrea Quintanilla, Kieran Wynne, Aleksandar Krstic, Juan Carlos Acosta, Cormac Taylor, Susanne Schlisio, Alex von Kriegsheim
Cellular p53 protein levels are regulated by a ubiquitination/de-ubiquitination cycle that can target the protein for proteasomal destruction. The ubiquitination reaction is catalyzed by a multitude of ligases, whereas the removal of ubiquitin chains is mediated by two deubiquitinating enzymes (DUBs), USP7 (HAUSP) and USP10. Here, we show that PHD3 hydroxylates p53 at proline 359, a residue that is in the p53-DUB binding domain. Hydroxylation of p53 upon proline 359 regulates its interaction with USP7 and USP10, and its inhibition decreases the association of p53 with USP7/USP10, increases p53 ubiquitination, and rapidly reduces p53 protein levels independently of mRNA expression...
July 31, 2018: Cell Reports
Chang Lu, Zhen Ning, Aman Wang, Di Chen, Xiaolong Liu, Tian Xia, Dinesh Singh Tekcham, Wen Wang, Tongming Li, Xiumei Liu, Jing Liu, Huan Qi, Haifeng Luo, Jian Du, Chi Ma, Qiu Yan, Jiwei Liu, Guowang Xu, Hai-Long Piao, Guang Tan
Dysregulation of deubiquitination pathway is associated with poor prognosis in cancers such as hepatocellular carcinoma (HCC). The mammalian target of rapamycin, mTOR, has become an attractive cancer therapeutic target in HCC. However, whether and how aberrant expression of deubiquitination pathway regulates mTOR pathway has remained elusive. Here we report that ubiquitin-specific protease 10 (USP10) functions as a tumor suppressor which inhibits mTOR pathway by stabilizing PTEN and AMPKα in HCC cells. Mechanistically, USP10 interacts and stabilizes PTEN and AMPKα by inhibiting their polyubiquitylation...
November 1, 2018: Cancer Letters
FangLiang Zhang, YuLong Li, Lin Chen, Jia Cheng, Ping Wu, WuYing Chu, JianShe Zhang
Skeletal muscle atrophy results from fasting, disuse and other systemic diseases. Muscle atrophy is associated with increased muscle protein degradation via the Ubiquitin proteasome system (UPS). The Ubiquitin Specific Proteases (USPs), also known as deubiquitinating enzymes, regulates a wide variety of cellular processes in skeletal muscle. In our study, among the 41 members of the USP family identified in the skeletal muscle transcriptome of Chinese perch, 24 USPs were differentially expressed between the fast and slow muscle fibers...
November 30, 2018: Gene
Amanda Tomie Ouchida, Merve Kacal, Adi Zheng, Gorbatchev Ambroise, Boxi Zhang, Erik Norberg, Helin Vakifahmetoglu-Norberg
Epithelial-to-mesenchymal transition (EMT) is a fundamental mechanism governing the switch of cells from an epithelial to a motile mesenchymal-like state. This transdifferentiation is regulated by key transcription factors, including Slug. The stability and function of Slug can be regulated by multiple mechanisms, including ubiquitin-mediated post-translational modifications. Here, by using a genome wide siRNA screen for human deubiquitinating enzymes (DUBs), we identified USP10 as a deubiquitinase for Slug in cancer cells...
August 25, 2018: Biochemical and Biophysical Research Communications
Pengcheng Luo, Cong Qin, Lihua Zhu, Chun Fang, Yan Zhang, Hai Zhang, Fei Pei, Song Tian, Xue-Yong Zhu, Jun Gong, Qing Mao, Chengcheng Xiao, Yang Su, Haizhou Zheng, Tao Xu, Jingxiao Lu, Jie Zhang
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation, and the pathogenic mechanism of NAFLD is poorly understood. Ubiquitin-specific peptidase 10 (USP10), a member of the ubiquitin-specific protease family, is involved in environmental stress responses, tumor growth, inflammation, and cellular metabolism. However, the role of USP10 in hepatic steatosis, insulin resistance, and inflammation remains largely unexplored. USP10 expression was detected in livers of patients with NAFLD, mice with high-fat diet (HFD)-induced obesity, and genetically obese (ob/ob) mice, as well as in palmitate-induced hepatocytes...
April 26, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xing-Chun Peng, Zhi Zeng, Yu-Ning Huang, Yun-Chao Deng, Guo-Hui Fu
Transmembrane-4-L-six-family member-1 (TM4SF1), a tumor-associated antigen, is overexpressed in most epithelial cell carcinomas and a potential target for antibody-mediated therapy. However, the role of TM4SF1 in gastric cancer has not been elucidated. The aim of this study was to investigate the clinical significance of TM4SF1 expression in gastric carcinoma (GC) tissues using 152 GC tissue samples and matched adjacent nontumor tissue samples analyzed by immunohistochemistry, and 13 fresh GC tissue samples analyzed by Western blotting...
June 2018: Cancer Medicine
Aram Ko, Su Yeon Han, Chel Hun Choi, Hanbyoul Cho, Min-Sik Lee, Soo-Youl Kim, Joon Seon Song, Kyeong-Man Hong, Han-Woong Lee, Stephen M Hewitt, Joon-Yong Chung, Jaewhan Song
Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10)...
June 2018: Cell Death and Differentiation
Ken-Ichi Takayama, Takashi Suzuki, Tetsuya Fujimura, Satoru Takahashi, Satoshi Inoue
Ubiquitin-specific protease 10 (USP10) is known to deubiquitylate its target proteins, mainly to enhance their stabilities. USP10 maintains p53 protein levels and controls epigenetic changes induced by the androgen receptor (AR). GTPase-activating protein-binding protein 2 (G3BP2), an androgen-responsive gene, is known as the main component of stress granules (SG) that interacts with USP10 in SGs. This study explores the roles of USP10 in prostate cancer progression in p53, G3BP2, and AR signaling. Using chromatin immunoprecipitation (ChIP) and sequence analysis, it was found that USP10 is transcriptionally induced with AR recruitment to an intronic region...
May 2018: Molecular Cancer Research: MCR
Wei Zhao, Dan Lu, Liang Liu, Juan Cai, Yu Zhou, Ying Yang, Yu Zhang, Jun Zhang
Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3/IMP3/KOC), initially identified as an RNA-binding protein, is highly expressed in embryonic tissues and a variety of cancers. Previously, our group reported that IGF2BP3 may serve as a potential diagnostic marker for lung cancer. However, little is known about the function of IGF2BP3 in lung cancer development. Here we demonstrate that IGF2BP3 expression was markedly increased in lung cancer tissues compared to normal tissues at both mRNA and protein levels...
November 7, 2017: Oncotarget
Youjin Jung, Hag Dong Kim, Hee Woong Yang, Hye Jin Kim, Chang-Young Jang, Joon Kim
When a ribosome complex is stalled during the translation elongation process in eukaryotes, the mono-ubiquitination of Rps3 has recently been shown to be critical to ribosome quality control. We have discovered that the regulatory role of Rps3 mono-ubiquitination is controlled by a deubiquitinase. We also showed that an autophagic signal appears to be coupled to the mono-ubiquitination of Rps3p through the entrance of Ubp3p into the autophagosome in yeasts. The mono-ubiquitination of the Rps3 protein is tightly modulated by reciprocal action between the Hel2p E3 ligase and the Ubp3p deubiquitinase in yeasts and the reciprocal action between the RNF123 E3 ligase and the USP10 deubiquitinase in mammalian cells...
November 17, 2017: Experimental & Molecular Medicine
A Emilia Arguello, Amanda N DeLiberto, Ralph E Kleiner
Epitranscriptomic RNA modifications can regulate mRNA function; however, there is a major gap in our understanding of the biochemical mechanisms mediating their effects. Here, we develop a chemical proteomics approach relying upon photo-cross-linking with synthetic diazirine-containing RNA probes and quantitative proteomics to profile RNA-protein interactions regulated by N6 -methyladenosine (m6 A), the most abundant internal modification in eukaryotic RNA. In addition to identifying YTH domain-containing proteins and ALKBH5, known interactors of this modification, we find that FMR1 and LRPPRC, two proteins associated with human disease, "read" this modification...
December 6, 2017: Journal of the American Chemical Society
Ellen L Weisberg, Nathan J Schauer, Jing Yang, Ilaria Lamberto, Laura Doherty, Shruti Bhatt, Atsushi Nonami, Chengcheng Meng, Anthony Letai, Renee Wright, Hong Tiv, Prafulla C Gokhale, Maria Stella Ritorto, Virginia De Cesare, Matthias Trost, Alexandra Christodoulou, Amanda Christie, David M Weinstock, Sophia Adamia, Richard Stone, Dharminder Chauhan, Kenneth C Anderson, Hyuk-Soo Seo, Sirano Dhe-Paganon, Martin Sattler, Nathanael S Gray, James D Griffin, Sara J Buhrlage
Oncogenic forms of the kinase FLT3 are important therapeutic targets in acute myeloid leukemia (AML); however, clinical responses to small-molecule kinase inhibitors are short-lived as a result of the rapid emergence of resistance due to point mutations or compensatory increases in FLT3 expression. We sought to develop a complementary pharmacological approach whereby proteasome-mediated FLT3 degradation could be promoted by inhibitors of the deubiquitinating enzymes (DUBs) responsible for cleaving ubiquitin from FLT3...
December 2017: Nature Chemical Biology
Ann P Lawson, Daniel W Bak, D Alexander Shannon, Marcus J C Long, Tushara Vijaykumar, Runhan Yu, Farid El Oualid, Eranthie Weerapana, Lizbeth Hedstrom
Cruciferous vegetables such as broccoli and kale have well documented chemopreventative and anticancer effects that are attributed to the presence of isothiocyanates (ITCs). ITCs modulate the levels of many oncogenic proteins, but the molecular mechanisms of ITC action are not understood. We previously reported that phenethyl isothiocyanate (PEITC) inhibits two deubiquitinases (DUBs), USP9x and UCH37. DUBs regulate many cellular processes and DUB dysregulation is linked to the pathogenesis of human diseases including cancer, neurodegeneration, and inflammation...
August 1, 2017: Oncotarget
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...
April 2018: Molecular and Cellular Biochemistry
Stephanie R Gillespie, Liana J Tedesco, Lingyan Wang, Audrey M Bernstein
Scarring and fibrotic disease result from the persistence of myofibroblasts characterized by high surface expression of αv integrins and subsequent activation of the transforming growth factor β (TGFβ) proteins; however, the mechanism controlling their surface abundance is unknown. Genetic screening revealed that human primary stromal corneal myofibroblasts overexpress a subset of deubiquitylating enzymes (DUBs), which remove ubiquitin from proteins, preventing degradation. Silencing of the DUB USP10 induces a buildup of ubiquitin on integrins β1 and β5 in cell lysates, whereas recombinant USP10 removes ubiquitin from these integrin subunits...
October 15, 2017: Journal of Cell Science
Matthew A Romero, C Brooks Mobley, Melissa A Linden, Grace Margaret-Eleanor Meers, Jeffrey S Martin, Kaelin C Young, R Scott Rector, Michael D Roberts
OBJECTIVE: The purpose of this study was to examine if: (a) high sugar/high fat Western diet (WD)-feeding affects skeletal muscle ribosome biogenesis markers in hyperphagic, diabetic-prone Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and (b) 12 weeks of treadmill training rescued potential detriments that WD feeding exerted on these markers. METHODS: Eight week-old male OLETF rats were fed a low-fat control diet (O-CON, n = 10) or high/sucrose/cholesterol Western diet (WD)...
August 11, 2017: BMC Research Notes
Wei Zhang, Maria A Sartori, Taras Makhnevych, Kelly E Federowicz, Xiaohui Dong, Li Liu, Satra Nim, Aiping Dong, Jingsong Yang, Yanjun Li, Dania Haddad, Andreas Ernst, Dirk Heerding, Yufeng Tong, Jason Moffat, Sachdev S Sidhu
Post-translational modification of the p53 signaling pathway plays an important role in cell cycle progression and stress-induced apoptosis. Indeed, a large body of work has shown that dysregulation of p53 and its E3 ligase MDM2 by the ubiquitin-proteasome system (UPS) promotes carcinogenesis and malignant transformation. Thus, drug discovery efforts have focused on the restoration of wild-type p53 activity or inactivation of oncogenic mutant p53 by targeted inhibition of UPS components, particularly key deubiquitinases (DUBs) of the ubiquitin-specific protease (USP) class...
November 10, 2017: Journal of Molecular Biology
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