keyword
https://read.qxmd.com/read/38518599/utilizing-machine-learning-to-identify-nifuroxazide-as-an-inhibitor-of-ubiquitin-specific-protease-21-in-a-drug-repositioning-strategy
#1
JOURNAL ARTICLE
Jihoon Tak, Tan Khanh Nguyen, Kyeong Lee, Sang Geon Kim, Hee-Chul Ahn
Ubiquitin-specific protease (USP), an enzyme catalyzing protein deubiquitination, is involved in biological processes related to metabolic disorders and cancer proliferation. We focused on constructing predictive models tailored to unveil compounds boasting USP21 inhibitory attributes. Six models, Extra Trees Classifier, Random Forest Classifier, LightGBM Classifier, XGBoost Classifier, Bagging Classifier, and a convolutional neural network harnessed from empirical data were selected for the screening process...
March 21, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38439981/tet2-stabilized-by-deubiquitinase-usp21-ameliorates-cigarette-smoke-induced-apoptosis-in-airway-epithelial-cells
#2
JOURNAL ARTICLE
Lijuan Luo, Zihang Zeng, Tiao Li, Xiangming Liu, Yanan Cui, Yongguang Tao, Yi Li, Yan Chen
DNA demethylase TET2 was related with lung function. However, the precise role of TET2 in cigarette smoke (CS)-induced apoptosis of airway epithelium cells, and the mechanisms involved, have yet to be elucidated. Here, we showed that CS decreased TET2 protein levels but had no significant effect on its mRNA levels in lung tissues of chronic obstructive pulmonary disease (COPD) patients and CS-induced COPD mice model and even in airway epithelial cell lines. TET2 could inhibit CS-induced apoptosis of airway epithelial cell in vivo and in vitro ...
March 15, 2024: IScience
https://read.qxmd.com/read/38385089/usp21-deubiquitinates-and-stabilizes-hsp90-and-eno1-to-promote-aerobic-glycolysis-and-proliferation-in-cholangiocarcinoma
#3
JOURNAL ARTICLE
Xiao Xu, Yananlan Chen, Shenye Shao, Jifei Wang, Jijun Shan, Yuming Wang, Yirui Wang, Jiang Chang, Tao Zhou, Ruixiang Chen, Shuochen Liu, Chang Li, Changxian Li, Xiangcheng Li
Deubiquitylating enzymes (DUBs) play an essential role in targeted protein degradation and represent an emerging therapeutic paradigm in cancer. However, their therapeutic potential in cholangiocarcinoma (CCA) has not been explored. Herein, based on The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) databases, we found that ubiquitin-specific protease 21 (USP21) was upregulated in CCA, high USP21 level was associated with poor prognosis. In vivo and in vitro, we identified USP21 as a master regulator of CCA growth and maintenance, which directly interacted with deubiquitinates and stabilized the heat shock protein 90 (HSP90) through K48-linked deubiquitination, and in turn, this stabilization increased HIF1A expression, thus upregulating key glycolytic enzyme genes ENO2, ENO3, ALDOC, ACSS2, and then promoted aerobic glycolysis, which provided energy for CCA cell proliferation...
2024: International Journal of Biological Sciences
https://read.qxmd.com/read/38302849/exploration-of-diagnostic-deubiquitinating-enzymes-in-endometriosis-and-its-immune-infiltration
#4
JOURNAL ARTICLE
Xinyun Yang, Kai Yan, Qitao Zhan, Hao Chen, Chang-Zhu Pei, Linling Zhu
The mechanism involved in the pathogenesis of endometriosis is poorly understood. The purpose of this study is to identify key deubiquitinating enzymes (DUBs) for endometriosis diagnosis and elucidate the possible mechanism, offering novel insights for noninvasive early diagnosis and treatment. Four gene expression datasets were employed from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) between endometriosis and normal controls. GO and KEGG pathways were performed for enrichment analysis...
February 1, 2024: Biochemical Genetics
https://read.qxmd.com/read/38298234/retracted-usp21-promotes-the-progression-of-nasopharyngeal-carcinoma-by-regulating-foxm1
#5
Stem Cells International
[This retracts the article DOI: 10.1155/2023/9196583.].
2024: Stem Cells International
https://read.qxmd.com/read/38292422/circcd2ap-promotes-epithelial-mesenchymal-transition-and-stemness-in-bladder-cancer-by-regulating-foxq1-usp21-axis
#6
JOURNAL ARTICLE
Jinrong Wang, Jing Tan, Yichuan Zhang, Lei Zhou, Yuan Liu
Bladder cancer (BC) is a prevalent and deadly disease. circCD2AP was suggested to be highly expressed in BC. However, the exact mechanism needs further investigation. In this study, circCD2AP was observed to be upregulated in BC and linked to poor prognosis in individuals. Functionally, circCD2AP or USP21 knockdown inhibited BC cell EMT and stemness both in vitro and in vivo . Mechanistically, circCD2AP interacted with ELAVL1 to enhance the stability of USP21 mRNA, which, in turn, inhibited the ubiquitination degradation of FOXQ1...
February 16, 2024: IScience
https://read.qxmd.com/read/38250150/ubiquitin-specific-protease-35-promotes-gastric-cancer-metastasis-by-increasing-the-stability-of-snail1
#7
JOURNAL ARTICLE
Cunying Ma, Zhuangfei Tian, Dandan Wang, Wenrong Gao, Lilin Qian, Yichen Zang, Xia Xu, Jihui Jia, Zhifang Liu
Deubiquitinase (DUB) dysregulation is closely associated with multiple diseases, including tumors. In this study, we used data from The Cancer Genome Atlas and Gene Expression Omnibus databases to analyze the expression of 51 ubiquitin-specific proteases (USPs) in gastric cancer (GC) tissues and adjacent non-neoplastic tissues. The Kaplan-Meier Plotter database was used to analyze the association of the differentially expressed USPs with the overall survival of patients with GC. The results showed that five USPs (USP5, USP10, USP13, USP21, and USP35) were highly expressed in GC tissues and were associated with poor prognosis in patients with GC...
2024: International Journal of Biological Sciences
https://read.qxmd.com/read/38170790/guanosine-diphosphate-mannose-suppresses-homologous-recombination-repair-and-potentiates-antitumor-immunity-in-triple-negative-breast-cancer
#8
JOURNAL ARTICLE
Jia-Han Ding, Yi Xiao, Fan Yang, Xiao-Qing Song, Ying Xu, Xiao-Hong Ding, Rui Ding, Zhi-Ming Shao, Gen-Hong Di, Yi-Zhou Jiang
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis. TNBCs with high homologous recombination deficiency (HRD) scores benefit from DNA-damaging agents, including platinum drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, whereas those with low HRD scores still lack therapeutic options. Therefore, we sought to exploit metabolic alterations to induce HRD and sensitize DNA-damaging agents in TNBCs with low HRD scores. We systematically analyzed TNBC metabolomics and identified a metabolite, guanosine diphosphate (GDP)-mannose (GDP-M), that impeded homologous recombination repair (HRR)...
January 3, 2024: Science Translational Medicine
https://read.qxmd.com/read/37990144/probable-human-origin-of-the-sars-cov-2-polybasic-furin-cleavage-motif
#9
JOURNAL ARTICLE
Antonio R Romeu
BACKGROUND: The key evolutionary step leading to the pandemic virus was the acquisition of the PRRA furin cleavage motif at the spike glycoprotein S1/S2 junction by a progenitor of SARS-CoV-2. Two of its features draw attention: (i) it is absent in other known lineage B beta-coronaviruses, including the newly discovered coronaviruses in bats from Laos and Vietnam, which are the closest known relatives of the covid virus; and, (ii) it introduced the pair of arginine codons (CGG-CGG), whose usage is extremely rare in coronaviruses...
November 21, 2023: BMC genomic data
https://read.qxmd.com/read/37964466/inhibition-of-usp21-leads-to-ovarian-carcinoma-cell-death-by-suppressing-mapk-signaling
#10
JOURNAL ARTICLE
Xin Sun, Jia Yu, Xiaorong Cui, Yujie Tang, Yani Yu
Ovarian cancer is the most aggressive and lethal of all gynecologic malignancies. Although the overexpression (OE) of ubiquitin-specific peptidase 21 (USP21) has been observed in multiple cancers, its expression profile and biological function in ovarian cancer remain unknown. The expression levels of USP21 in ovarian cancer cells and tissues as well as adjacent normal tissues were assessed by qRT-PCR or Western blot assay. The biological function of USP21 in ovarian cancer cells was assessed by cell growth assay in vitro and a tumor growth model in vivo...
November 14, 2023: Biotechnology and Applied Biochemistry
https://read.qxmd.com/read/37875823/exploration-and-validation-of-a-novel-signature-of-seven-necroptosis-related-genes-to-improve-the-clinical-outcome-of-hepatocellular-carcinoma
#11
JOURNAL ARTICLE
Qiqi Tao, Zhichao Lang, Yifei Li, Yuxiang Gao, Lifan Lin, Zhengping Yu, Jianjian Zheng, Suhui Yu
Necroptosis has been reported to be involved in cancer progression and associated with cancer prognosis. However, the prognostic values of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to build a signature on the basis of NRGs to evaluate the prognosis of HCC patients. In this study, using bioinformatic analyses of transcriptome sequencing data of HCC (n = 370) from The Cancer Genome Atlas (TCGA) database, 63 differentially expressed NRGs between HCC and adjacent normal tissues were determined...
October 24, 2023: BMC Cancer
https://read.qxmd.com/read/37828052/polarity-protein-af6-functions-as-a-modulator-of-necroptosis-by-regulating-ubiquitination-of-ripk1-in-liver-diseases
#12
JOURNAL ARTICLE
Wang Xinyu, Wen Qian, Wu Yanjun, Kong Jingwen, Xu Keying, Jiao Jiazheng, Zhang Haibing, Wang Kai, Xu Xiao, Zhan Lixing
AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing to cell-cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS)...
October 12, 2023: Cell Death & Disease
https://read.qxmd.com/read/37743467/synergistic-effect-of-yod1-and-usp21-on-the-hippo-signaling-pathway
#13
JOURNAL ARTICLE
Sang-Soo Park, Kwang-Hyun Baek
BACKGROUND: Deubiquitinating enzymes (DUBs) comprise a family of proteases responsible for cleaving the peptide or isopeptide bond between ubiquitin and its substrate proteins. Ubiquitin is essential for regulating diverse cellular functions by attaching to target proteins. The Hippo signaling pathway plays a crucial role in controlling tissue size, cell proliferation, and apoptosis. In a previous study, we discovered that YOD1 regulates the Hippo signaling pathway by deubiquitinating the neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ligase of large tumor suppressor kinase 1 (LATS1)...
September 24, 2023: Cancer Cell International
https://read.qxmd.com/read/37434557/c-jun-induced-upregulation-of-linc00174-contributes-to-colorectal-cancer-proliferation-and-invasion-through-accelerating-usp21-expression
#14
JOURNAL ARTICLE
Weijie Liang, Dongdong Liu, Jie Wu
Colorectal cancer (CRC) is one of the most common human malignancies due to its invasiveness and metastasis. Recent studies revealed the pivotal roles of long noncoding RNAs (lncRNAs) in tumorigenesis and progressions of various tumors. However, the biological roles and molecular mechanisms of long intergenic noncoding RNA 00174 (LINC00174) in human CRC remain unclear. Here, we report that LINC00174 expression was higher in human CRC tissues and cell lines than in adjacent normal tissues and a colon epithelial cell line (FHC)...
July 12, 2023: Cell Biology International
https://read.qxmd.com/read/37096811/design-and-development-of-novel-potential-inhibitors-of-the-human-usp21-enzyme-using-a-pharmacophore-based-virtual-screening-technique
#15
JOURNAL ARTICLE
Alankar Roy, Shreya Luharuka, Ishani Paul, Sujay Ray
An overexpression and increase have been observed in the concentration and activity of the USP21 enzyme in many cancers, necessitating the need for the development of new inhibitor drugs against the same. The current study attempts to discover one such novel potential inhibitor of USP21 by the application of various bioinformatics techniques which include molecular modelling, pharmacophore mapping, and pharmacophore-based virtual screening, molecular docking, and ADMET prediction followed by molecular dynamics simulations...
April 25, 2023: Journal of Molecular Recognition: JMR
https://read.qxmd.com/read/36919585/usp21-contributes-to-the-aggressiveness-of-laryngeal-cancer-cells-by-deubiquitinating-and-stabilizing-aurka
#16
JOURNAL ARTICLE
Qing-Dong Wang, Tao Shi, Yang Xu, Yang Liu, Mei-Jia Zhang
Laryngeal cancer is a usual malignant tumor of the head and neck. The role and mechanism of deubiquitinase USP21 in laryngeal cancer are still unclear. We aimed to explore whether USP21 affected laryngeal cancer progress through deubiquitinating AURKA. USP21 and AURKA levels were evaluated by qRT-PCR and Western blot. Kaplan-Meier analysis was conducted by survival package. MTT was performed to detect cell proliferation. The wound healing assay was applied to evaluate cell migration. Transwell was used to measure cell invasion...
March 15, 2023: Kaohsiung Journal of Medical Sciences
https://read.qxmd.com/read/36834633/ubiquitin-specific-proteases-usps-and-metabolic-disorders
#17
REVIEW
Hiroshi Kitamura
Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and enzymatic activity. Ubiquitin-specific proteases (USPs) constitute the largest deubiquitinating enzyme family. To date, accumulating evidence indicates that several USPs positively and negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia...
February 6, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36820242/usp21-promotes-the-progression-of-nasopharyngeal-carcinoma-by-regulating-foxm1
#18
JOURNAL ARTICLE
Xiaofeng Li, Xia Li
The purpose of this work was to explore the molecular mechanisms by which USP21 regulates nasopharyngeal carcinoma tumor growth and cancer cell stemness. In this study, the USP21 transcript data was obtained from TCGA database. Then, qPCR and western blot tests revealed that, in contrast to normal tissue or normal nasopharyngeal epithelial cells, the expression of USP21 was greater in nasopharyngeal carcinoma tissues or cell lines, respectively. CCK-8 and EdU immunofluorescent staining assays revealed that USP21 promoted the proliferation of nasopharyngeal carcinoma cells...
2023: Stem Cells International
https://read.qxmd.com/read/36802665/discovery-and-characterization-of-bay-805-a-potent-and-selective-inhibitor-of-ubiquitin-specific-protease-usp21
#19
JOURNAL ARTICLE
Fabian Göricke, Victoria Vu, Leanna Smith, Ulrike Scheib, Raphael Böhm, Namik Akkilic, Gerd Wohlfahrt, Jörg Weiske, Ulf Bömer, Krzysztof Brzezinka, Niels Lindner, Philip Lienau, Stefan Gradl, Hartmut Beck, Peter J Brown, Vijayaratnam Santhakumar, Masoud Vedadi, Dalia Barsyte-Lovejoy, Cheryl H Arrowsmith, Norbert Schmees, Kirstin Petersen
USP21 belongs to the ubiquitin-specific protease (USP) subfamily of deubiquitinating enzymes (DUBs). Due to its relevance in tumor development and growth, USP21 has been reported as a promising novel therapeutic target for cancer treatment. Herein, we present the discovery of the first highly potent and selective USP21 inhibitor. Following high-throughput screening and subsequent structure-based optimization, we identified BAY-805 to be a non-covalent inhibitor with low nanomolar affinity for USP21 and high selectivity over other DUB targets as well as kinases, proteases, and other common off-targets...
February 20, 2023: Journal of Medicinal Chemistry
https://read.qxmd.com/read/36764771/antibody-free-approach-for-ubiquitination-profiling-by-selectively-clicking-the-ubiquitination-sites
#20
JOURNAL ARTICLE
Mingwei Sun, Qing Zhang, Baofeng Zhao, Qiuling Huang, Wenfeng Wu, Peiyang Fan, Lihua Zhang, Xiaofei Zhang
Ubiquitination is a reversible post-translational modification that plays a pivotal role in numerous biological processes. Antibody-based approaches, as the most used methods for identifying ubiquitination sites, exist sequence recognition bias, high cost, and ubiquitin-like protein modification interference, limiting their widespread application. Here, we proposed an Antibody-Free approach for Ubiquitination Profiling, termed AFUP, by selectively clicking the ubiquitinated lysine to enrich and profile endogenous ubiquitinated peptides using mass spectrometry...
March 15, 2023: Analytica Chimica Acta
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