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Deubiquitinase

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https://www.readbyqxmd.com/read/28637794/a-trpv1-to-secretagogin-regulatory-axis-controls-pancreatic-%C3%AE-cell-survival-by-modulating-protein-turnover
#1
Katarzyna Malenczyk, Fatima Girach, Edit Szodorai, Petter Storm, Åsa Segerstolpe, Giuseppe Tortoriello, Robert Schnell, Jan Mulder, Roman A Romanov, Erzsébet Borók, Fabiana Piscitelli, Vincenzo Di Marzo, Gábor Szabó, Rickard Sandberg, Stefan Kubicek, Gert Lubec, Tomas Hökfelt, Ludwig Wagner, Leif Groop, Tibor Harkany
Ca(2+)-sensor proteins are generally implicated in insulin release through SNARE interactions. Here, secretagogin, whose expression in human pancreatic islets correlates with their insulin content and the incidence of type 2 diabetes, is shown to orchestrate an unexpectedly distinct mechanism. Single-cell RNA-seq reveals retained expression of the TRP family members in β-cells from diabetic donors. Amongst these, pharmacological probing identifies Ca(2+)-permeable transient receptor potential vanilloid type 1 channels (TRPV1) as potent inducers of secretagogin expression through recruitment of Sp1 transcription factors...
June 21, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28623188/gli1-induced-deubiquitinase-usp48-aids-glioblastoma-tumorigenesis-by-stabilizing-gli1
#2
Aidong Zhou, Kangyu Lin, Sicong Zhang, Li Ma, Jianfei Xue, Saint-Aaron Morris, Kenneth D Aldape, Suyun Huang
Aberrant activation of the Hedgehog (Hh) signaling pathway drives the tumorigenesis of multiple cancers. In this study, we screened a panel of deubiquitinases that may regulate the Hh pathway. We find that deubiquitinase USP48 activates Gli-dependent transcription by stabilizing Gli1 protein. Mechanistically, USP48 interacts with Gli1 and cleaves its ubiquitin off directly. In glioblastoma cells, knockdown of USP48 inhibits cell proliferation and the expression of Gli1's downstream targets, which leads to repressed glioblastoma tumorigenesis...
June 16, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28620049/the-x-linked-deubiquitinase-usp9x-is-an-integral-component-of-centrosome
#3
Qian Wang, Yiman Tang, Yue Xu, Shilei Xu, Yong Jiang, Qiuping Dong, Yongsheng Zhou, Wenshu Ge
The X-linked deubiquitinase USP9X has been implicated in multiple pathological disorders including malignancies and X-linked intellectual disability. However, its biological function and substrate repertoire remain to be investigated. In this study, we utilized the TMT (tandem mass tags) labeling assay to identify USP9X regulated proteins, and revealed that the expression of multiple genes is altered in USP9X deficient cells. Interestingly, we showed that USP9X promotes stabilization of centrosome protein PCM1 and CEP55 through its catalytic activity...
June 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28619062/platinum-containing-compound-platinum-pyrithione-suppresses-ovarian-tumor-proliferation-through-proteasome-inhibition
#4
Hongbiao Huang, Ni Liu, Yuning Liao, Ningning Liu, Jianyu Cai, Xiaohong Xia, Zhiqiang Guo, Yanling Li, Qirong Wen, Qi Yin, Yan Liu, Qingxia Wu, Dhivya Rajakumar, Xiujie Sheng, Jinbao Liu
BACKGROUND: Ovarian carcinoma is one of the most aggressive gynecological malignant neoplasms and makes up 25-30% of all cancer cases of the female genital tract. Currently, resistance to traditional chemotherapy is a great challenge for patients with Epithelial ovarian cancer (EOC). Therefore, identifying novel agents for EOC treatment is essential and urgent. METHOD: MTS assay was used to analyze the cell viability and proliferation of cancer cells. Flow cytometry was employed to analyze cell cycle distribution and cell apoptosis...
June 15, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28617443/bilirubin-neurotoxicity-is-associated-with-proteasome-inhibition
#5
Hongbiao Huang, Mingxing Guo, Ningning Liu, Chong Zhao, Haoyu Chen, Xiaoli Wang, Siyan Liao, Ping Zhou, Yuning Liao, Xin Chen, Xiaoying Lan, Jinghong Chen, Dacai Xu, Xiaofen Li, Xianping Shi, Li Yu, Yuqiang Nie, Xuejun Wang, Chang-E Zhang, Jinbao Liu
The molecular mechanism underlying bilirubin neurotoxicity remains obscure. Ubiquitin-proteasome system-mediated proteolysis is pivotal to virtually all cellular processes and cell survival. Here we report for the first time that bilirubin at a clinically relevant elevated level impairs proteasomal function via inhibiting both the 19S proteasome-associated deubiquitinases (USP14 and UCHL5) and the chymotrypsin-like (CT-like) peptidase activity of 20S proteasomes, thereby contributing to bilirubin neurotoxicity...
June 15, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28587923/generation-and-validation-of-intracellular-ubiquitin-variant-inhibitors-for-usp7-and-usp10
#6
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...
June 3, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28587922/molecular-basis-for-k63-linked-ubiquitination-processes-in-double-strand-dna-break-repair-a-focus-on-kinetics-and-dynamics
#7
REVIEW
Brian L Lee, Anamika, J N Mark Glover, Michael J Hendzel, Leo Spyracopoulos
Cells are exposed to thousands of DNA damage events on a daily basis. This damage must be repaired to preserve genetic information, and prevent development of disease. The most deleterious damage is a double strand break (DSB), which is detected and repaired by mechanisms known as non-homologous end joining (NHEJ), and homologous recombination (HR), components of the DNA damage response system. NHEJ is an error prone first line of defense, whereas HR invokes error free repair, and is the focus of this review...
June 3, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28583475/ubiquitin-c-terminal-hydrolase-l3-promotes-interferon-antiviral-activity-by-stabilizing-type-i-interferon-receptor
#8
Peng Zhao, Tingting Guo, Liping Qian, Xiaofang Wang, Yukang Yuan, Qiao Cheng, Yibo Zuo, Jin Liu, Ying Miao, Qian Feng, Liting Zhang, Shuhua Wu, Hui Zheng
Type-I interferons (IFN-I) are important antiviral drugs which are widely used in clinical therapy of diverse viral infections. However, understanding the detailed mechanisms for IFN-I antiviral signaling remains a major challenge, and may provide novel targets for IFN-based antiviral therapy. So far, the roles of deubiquitinases (DUBs) in regulating IFN-I antiviral activity are still largely unexplored. Here, we find that Ubiquitin C-terminal hydrolase-L3 (UCHL3) plays an important role in regulating type I-interferon (IFN-I) mediated antiviral response...
June 3, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28580429/specific-targeting-of-the-deubiquitinase-and-e3-ligase-families-with-engineered-ubiquitin-variants
#9
REVIEW
Maryna Gorelik, Sachdev S Sidhu
The ubiquitin proteasome system (UPS) has garnered much attention due to its potential for the development of therapeutics. Following a successful clinical application of general proteasome inhibitors much effort has been devoted to targeting individual UPS components including E3 enzymes and deubiquitinases that control specificity of ubiquitination. Our group has developed a novel approach for targeting the UPS proteins using engineered ubiquitin variants (Ubvs). These drug-like proteins can serve as valuable tools to study biological function of UPS components and assist in the development of small molecules for clinical use...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28577894/proteolytic-control-of-regulated-necrosis
#10
REVIEW
Johaiber Fuchslocher Chico, Carina Saggau, Dieter Adam
Proteases control most of the physiological processes that occur in a cell. This particularly applies to apoptosis, the most well-studied form of cell death, where proteolysis by cysteine-aspartic proteases (caspases) is the primary mechanism for both initiation and execution of cell suicide. In contrast, the impact of proteolysis on other, non-apoptotic cell death pathways (summarized under the term "regulated necrosis", RN) has long been enigmatic, but has clearly been confirmed by a number of recent groundbreaking discoveries...
May 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28572092/cyld-deubiquitinase-is-necessary-for-proper-ubiquitination-and-degradation-of-the-epidermal-growth-factor-receptor
#11
Virginia Sanchez-Quiles, Vyacheslav Akimov, Nerea Osinalde, Chiara Francavilla, Michele Puglia, Inigo Barrio-Hernandez, Irina Kratchmarova, Jesper V Olsen, Blagoy Blagoev
Cylindromatosis tumor suppressor protein (CYLD) is deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis...
June 1, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28570668/cooperative-inhibition-of-rip1-mediated-nf-%C3%AE%C2%BAb-signaling-by-cytomegalovirus-encoded-deubiquitinase-and-inactive-homolog-of-cellular-ribonucleotide-reductase-large-subunit
#12
Ki Mun Kwon, Se Eun Oh, Young Eui Kim, Tae-Hee Han, Jin-Hyun Ahn
Several viruses have been found to encode a deubiquitinating protease (DUB). These viral DUBs are proposed to play a role in regulating innate immune or inflammatory signaling. In human cytomegalovirus (HCMV), the largest tegument protein encoded by UL48 contains DUB activity, but its cellular targets are not known. Here, we show that UL48 and UL45, an HCMV-encoded inactive homolog of cellular ribonucleotide reductase (RNR) large subunit (R1), target receptor-interacting protein kinase 1 (RIP1) to inhibit NF-κB signaling...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28569838/usp13-regulates-the-rap80-brca1-complex-dependent-dna-damage-response
#13
Yunhui Li, Kuntian Luo, Yujiao Yin, Chenming Wu, Min Deng, Lei Li, Yuping Chen, Somaira Nowsheen, Zhenkun Lou, Jian Yuan
BRCA1 regulates multiple cellular pathways that maintain genomic stability including cell cycle checkpoints, DNA repair, protein ubiquitination, chromatin remodelling, transcriptional regulation and apoptosis. Receptor-associated protein 80 (RAP80) helps recruit BRCA1 to double-strand breaks (DSBs) through the scaffold protein CCDC98 (Abraxas) and facilitates DNA damage response (DDR). However, the regulation of RAP80-BRCA1 complex is still unclear. Here we report that a deubiquitinase, USP13, regulates DDR by targeting RAP80...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28559472/spermatogonial-deubiquitinase-usp9x-is-essential-for-proper-spermatogenesis-in-mice
#14
Kasane Kishi, Aya Uchida, Hinako M Takase, Hitomi Suzuki, Masamichi Kurohmaru, Naoki Tsunekawa, Masami Kanai-Azuma, Stephen A Wood, Yoshiakira Kanai
USP9X (ubiquitin-specific peptidase 9, X chromosome) is the mammalian orthologue of Drosophila deubiquitinase fat facets that was previously shown to regulate the maintenance of the germ cell lineage partially through stabilizing Vasa, one of the widely conserved factors crucial for gametogenesis. Here, we demonstrate that USP9X is expressed in the gonocytes and spermatogonia in mouse testes from newborn to adult stages. By using Vasa-Cre mice, germ cell-specific conditional deletion of Usp9x from the embryonic stage showed no abnormality in the developing testes by 1 week and no appreciable defects in the undifferentiated and differentiating spermatogonia at postnatal and adult stages...
August 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28557172/deubiquitinase-usp18-prevents-cellular-apoptosis-from-oxidative-stress-in-liver-cells
#15
Keng Po Lai, Angela Hoi Yan Cheung, William Ka Fai Tse
Deubiquitinases (DUBs) de-conjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate their activity and stability. They play different cellular functions such as cell cycle regulation, DNA repair and early embryogenesis. Additionally, studies have demonstrated that some DUBs are the signaling targets of cellular stress such as oxidative stress. Reactive oxygen species are generated during normal mitochondrial oxidative metabolism and proper cellular mechanism could protect the cell from the oxidative stress...
May 30, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28553951/post-translational-control-of-t-cell-development-by-the-escrt-protein-chmp5
#16
Stanley Adoro, Kwang Hwan Park, Sarah E Bettigole, Raphael Lis, Hee Rae Shin, Heewon Seo, Ju Han Kim, Klaus-Peter Knobeloch, Jae-Hyuck Shim, Laurie H Glimcher
The acquisition of a protective vertebrate immune system hinges on the efficient generation of a diverse but self-tolerant repertoire of T cells by the thymus through mechanisms that remain incompletely resolved. Here we identified the endosomal-sorting-complex-required-for-transport (ESCRT) protein CHMP5, known to be required for the formation of multivesicular bodies, as a key sensor of thresholds for signaling via the T cell antigen receptor (TCR) that was essential for T cell development. CHMP5 enabled positive selection by promoting post-selection thymocyte survival in part through stabilization of the pro-survival protein Bcl-2...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28544703/high-ubiquitin-specific-protease-44-expression-induces-dna-aneuploidy-and-provides-independent-prognostic-information-in-gastric-cancer
#17
Sho Nishimura, Eiji Oki, Koji Ando, Makoto Iimori, Yu Nakaji, Yuichiro Nakashima, Hiroshi Saeki, Yoshinao Oda, Yoshihiko Maehara
Chromosomal instability (CIN), characterized by aneuploidy, is a major molecular subtype of gastric cancer. The deubiquitinase USP44 is an important regulator of APC activation in the spindle checkpoint and leads to proper chromosome separation to prevent aneuploidy. Aberrant expression of USP44 leads CIN in cells; however, the correlation between USP44 and DNA aneuploidy in gastric cancer is largely unknown. We analyzed USP44 expression in 207 patients with gastric cancer by immunohistochemistry and found that the proportion of USP44 expression was higher in gastric cancer tumors (mean, 39...
June 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28542437/cp5-system-for-simple-and-highly-efficient-protein-purification-with-a-c-terminal-designed-mini-tag
#18
Hiroyuki Takeda, Wei Zhou, Kohki Kido, Ryoji Suno, Takahiro Iwasaki, Takuya Kobayashi, Tatsuya Sawasaki
There are many strategies to purify recombinant proteins of interest, and affinity purification utilizing monoclonal antibody that targets a linear epitope sequence is one of the essential techniques used in current biochemistry and structural biology. Here we introduce a new protein purification system using a very short CP5 tag. First, we selected anti-dopamine receptor D1 (DRD1) rabbit monoclonal antibody clone Ra62 (Ra62 antibody) as capture antibody, and identified its minimal epitope sequence as a 5-amino-acid sequence at C-terminal of DRD1 (GQHPT-COOH, D1CE sequence)...
2017: PloS One
https://www.readbyqxmd.com/read/28538147/structural-and-functional-investigations-of-the-n-terminal-ubiquitin-binding-region-of-usp25
#19
Yuanyuan Yang, Li Shi, Yiluan Ding, Yanhong Shi, Hong-Yu Hu, Yi Wen, Naixia Zhang
Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well...
May 23, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28535005/rpn11-deubiquitinase-promotes-proliferation-and-migration-of-breast-cancer-cells
#20
Guoqing Luo, Ningdong Hu, Xu Xia, Jingjing Zhou, Changsheng Ye
The deubiquitinase enzyme RPN11 is involved in oncogenesis in various types of cancer. However, in breast cancer, the expression levels, prognostic relevance and biological function of RPN11 remains unclear. In the present study, RPN11 expression levels in breast cancer tissues and adjacent non‑tumor tissues were determined by reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining, and the association of RPN11 with clinicopathological features of breast cancer was evaluated...
July 2017: Molecular Medicine Reports
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