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https://www.readbyqxmd.com/read/28236235/anchordock-for-blind-flexible-docking-of-peptides-to-proteins
#1
Michal Slutzki, Avraham Ben-Shimon, Masha Y Niv
Due to increasing interest in peptides as signaling modulators and drug candidates, several methods for peptide docking to their target proteins are under active development. The "blind" docking problem, where the peptide-binding site on the protein surface is unknown, presents one of the current challenges in the field. AnchorDock protocol was developed by Ben-Shimon and Niv to address this challenge.This protocol narrows the docking search to the most relevant parts of the conformational space. This is achieved by pre-folding the free peptide and by computationally detecting anchoring spots on the surface of the unbound protein...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#2
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/28157215/identification-of-a-genetically-defined-ultra-high-risk-group-in-relapsed-pediatric-t-lymphoblastic-leukemia
#3
P Richter-Pechańska, J B Kunz, J Hof, M Zimmermann, T Rausch, O R Bandapalli, E Orlova, G Scapinello, J C Sagi, M Stanulla, M Schrappe, G Cario, R Kirschner-Schwabe, C Eckert, V Benes, J O Korbel, M U Muckenthaler, A E Kulozik
In the search for genes that define critical steps of relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) and can serve as prognostic markers, we performed targeted sequencing of 313 leukemia-related genes in 214 patients: 67 samples collected at the time of relapse and 147 at initial diagnosis. As relapse-specific genetic events, we identified activating mutations in NT5C2 (P=0.0001, Fisher's exact test), inactivation of TP53 (P=0.0007, Fisher's exact test) and duplication of chr17:q11.2-24.3 (P=0...
February 3, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28137592/usp7-promotes-medulloblastoma-cell-survival-and-metastasis-by-activating-shh-pathway
#4
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/28108249/synthesis-and-biological-evaluation-of-thiazole-derivatives-as-novel-usp7-inhibitors
#5
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
https://www.readbyqxmd.com/read/28073915/ube2e1-ubch6-is-a-critical-in-vivo-e2-for-the-prc1-catalyzed-ubiquitination-of-h2a-at-lys-119
#6
Keith Wheaton, Feroz Sarkari, Beena Stanly Johns, Hossein Davarinejad, Olga Egorova, Lilia Kaustov, Brian Raught, Vivian Saridakis, Yi Sheng
UbE2E1/UbcH6 is an E2 ubiquitin-conjugating enzyme that is regulated by USP7. We identified UbE2E1 as a novel component of Polycomb repressive complex 1 (PRC1), the E3 ligase complex responsible for histone H2A ubiquitination and gene silencing. We demonstrate that UbE2E1 is critical for the monoubiquitination of H2A at residue Lys-119 (uH2AK119) through its association with the PRC1 complex. UbE2E1 interacts with PRC1 subunits including Ring1A and Ring1B. Overexpression of UbE2E1 results in increased levels of uH2AK119, whereas overexpression of catalytically inactive UbE2E1_C131A or UbE2E1 knockdown results in decreased levels of uH2AK119...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28061330/epop-interacts-with-elongin-bc-and-usp7-to-modulate-the-chromatin-landscape
#7
Robert Liefke, Violetta Karwacki-Neisius, Yang Shi
No abstract text is available yet for this article.
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28039431/data-integration-in-physiology-using-bayes-rule-and-minimum-bayes-factors-deubiquitylating-enzymes-in-the-renal-collecting-duct
#8
Zhe Xue, Jia-Xu Chen, Yue Zhao, Barbara Medvar, Mark A Knepper
A major challenge in physiology is to exploit the many large-scale datasets available from "-omic" studies in order to seek answers to key physiological questions. In previous studies, Bayes' Theorem has been used for this purpose. This approach requires a means to map continuously distributed experimental data to probabilities (likelihood values) in order to derive posterior probabilities from the combination of prior probabilities and new data. Here, we introduce the use of Minimum Bayes' Factors for this purpose and illustrate the approach by addressing a physiological question, "Which deubiquitylating enzymes (DUBs) encoded by mammalian genomes are most likely to regulate plasma membrane transport processes in renal cortical collecting duct principal cells?" To do this, we have created a comprehensive online database of 110 DUBs present in the mammalian genome (https://hpcwebapps...
December 30, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27934968/k63-polyubiquitinated-hausp-deubiquitinates-hif-1%C3%AE-and-dictates-h3k56-acetylation-promoting-hypoxia-induced-tumour-progression
#9
Han-Tsang Wu, Yi-Chih Kuo, Jung-Jyh Hung, Chi-Hung Huang, Wei-Yi Chen, Teh-Ying Chou, Yeh Chen, Yi-Ju Chen, Yu-Ju Chen, Wei-Chung Cheng, Shu-Chun Teng, Kou-Juey Wu
Intratumoural hypoxia induces HIF-1α and promotes tumour progression, metastasis and treatment resistance. HIF-1α stability is regulated by VHL-E3 ligase-mediated ubiquitin-dependent degradation; however, the hypoxia-regulated deubiquitinase that stabilizes HIF-1α has not been identified. Here we report that HAUSP (USP7) deubiquitinase deubiquitinates HIF-1α to increase its stability, induce epithelial-mesenchymal transition and promote metastasis. Hypoxia induces K63-linked polyubiquitinated HAUSP at lysine 443 to enhance its functions...
December 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/27927749/modulation-of-the-p53-mdm2-interplay-by-hausp-inhibitors
#10
REVIEW
Omid Tavana, Wei Gu
It is well established that both p53 and MDM2 are short-lived proteins whose stabilities are tightly controlled through ubiquitination-mediated degradation. Although numerous studies indicate that the MDM2 E3 ligase activity, as well as the protein-protein interaction between p53 and MDM2, is the major focus for this regulation, emerging evidence suggests that the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) plays a critical role. Furthermore, HAUSP inhibition elevates p53 stability and might be beneficial for therapeutic purposes...
December 6, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27863226/epop-interacts-with-elongin-bc-and-usp7-to-modulate-the-chromatin-landscape
#11
Robert Liefke, Violetta Karwacki-Neisius, Yang Shi
Gene regulatory networks are pivotal for many biological processes. In mouse embryonic stem cells (mESCs), the transcriptional network can be divided into three functionally distinct modules: Polycomb, Core, and Myc. The Polycomb module represses developmental genes, while the Myc module is associated with proliferative functions, and its mis-regulation is linked to cancer development. Here, we show that, in mESCs, the Polycomb repressive complex 2 (PRC2)-associated protein EPOP (Elongin BC and Polycomb Repressive Complex 2-associated protein; a...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27829160/disruption-of-the-phosphate-transporter-pit1-in-hepatocytes-improves-glucose-metabolism-and-insulin-signaling-by-modulating-the-usp7-irs1-interaction
#12
Anne Forand, Eugénie Koumakis, Alice Rousseau, Yohann Sassier, Clément Journe, Jean-François Merlin, Christine Leroy, Valérie Boitez, Patrice Codogno, Gérard Friedlander, Isabelle Cohen
No abstract text is available yet for this article.
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27780924/cddo-me-reveals-usp7-as-a-novel-target-in-ovarian-cancer-cells
#13
Dongjun Qin, Weiwei Wang, Hu Lei, Hao Luo, Haiyan Cai, Caixia Tang, Yunzhao Wu, Yingying Wang, Jin Jin, Weilie Xiao, Tongdan Wang, Chunmin Ma, Hanzhang Xu, Jinfu Zhang, Fenghou Gao, Ying-Li Wu
Deubiquitinating enzyme USP7 has been involved in the pathogenesis and progression of several cancers. Targeting USP7 is becoming an attractive strategy for cancer therapy. In this study, we identified synthetic triterpenoid C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid (CDDO-Me) as a novel inhibitor of USP7 but not of other cysteine proteases such as cathepsin B and cathepsin D. CDDO-Me inhibits USP7 activity via a mechanism that is independent of the presence of α, β-unsaturated ketones...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#14
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27752147/identification-of-reliable-reference-genes-for-qrt-pcr-studies-of-the-developing-mouse-mammary-gland
#15
Anoeska Agatha Alida van de Moosdijk, Renée van Amerongen
Cell growth and differentiation are often driven by subtle changes in gene expression. Many challenges still exist in detecting these changes, particularly in the context of a complex, developing tissue. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) allows relatively high-throughput evaluation of multiple genes and developmental time points. Proper quantification of gene expression levels by qRT-PCR requires normalization to one or more reference genes. Traditionally, these genes have been selected based on their presumed "housekeeping" function, with the implicit assumption that they are stably expressed over the entire experimental set...
October 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27667742/a-sumo-and-ubiquitin-code-coordinates-protein-traffic-at-replication-factories
#16
Emilio Lecona, Oscar Fernandez-Capetillo
Post-translational modifications regulate each step of DNA replication to ensure the faithful transmission of genetic information. In this context, we recently showed that deubiquitination of SUMO2/3 and SUMOylated proteins by USP7 helps to create a SUMO-rich and ubiquitin-low environment around replisomes that is necessary to maintain the activity of replication forks and for new origin firing. We propose that a two-flag system mediates the collective concentration of factors at sites of DNA replication, whereby SUMO and Ubiquitinated-SUMO would constitute "stay" or "go" signals respectively for replisome and accessory factors...
September 26, 2016: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/27663894/usp7-targeting-may-suppress-mycn-amplified-tumor-growth
#17
(no author information available yet)
USP7 deubiquitinates MYCN to enhance its stability and transcriptional activity in neuroblastoma.
September 23, 2016: Cancer Discovery
https://www.readbyqxmd.com/read/27632941/stabilization-of-lsd1-by-deubiquitinating-enzyme-usp7-promotes-glioblastoma-cell-tumorigenesis-and-metastasis-through-suppression-of-the-p53-signaling-pathway
#18
Lei Yi, Yan Cui, Qingfu Xu, Yugang Jiang
The substrates and mechanisms of ubiquitin specific peptidase 7 (USP7) in glioma remain unclear. Lysine‑specific demethylase 1 (LSD1) may undergo proteasomal degradation; however, a reciprocal mechanism that stabilizes LSD1 in glioma has not been dertermined. Here co-immunoprecipitation and GST pull-down assays revealed that LSD1 is associated with USP7 in vivo and in vitro. USP7 inhibited LSD1 ubiquitination and stabilized LSD1 in A172 and T98G cells. MTT, EdU proliferation, flow cytometry and Transwell assays indicated that LSD1 played a critical role in the proliferation and invasion of glioblastoma (GBM) cells...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27618649/hausp-deubiquitinates-and-stabilizes-n-myc-in-neuroblastoma
#19
Omid Tavana, Dawei Li, Chao Dai, Gonzalo Lopez, Debarshi Banerjee, Ning Kon, Chao Chen, Andrea Califano, Darrell J Yamashiro, Hongbin Sun, Wei Gu
The MYCN proto-oncogene is amplified in a number of advanced-stage human tumors, such as neuroblastomas. Similar to other members of the MYC family of oncoproteins, MYCN (also known as N-Myc) is a transcription factor, and its stability and activity are tightly controlled by ubiquitination-dependent proteasome degradation. Although numerous studies have demonstrated that N-Myc is a driver of neuroblastoma tumorigenesis, therapies that directly suppress N-Myc activity in human tumors are limited. Here we have identified ubiquitin-specific protease 7 (USP7; also known as HAUSP) as a regulator of N-Myc function in neuroblastoma...
October 2016: Nature Medicine
https://www.readbyqxmd.com/read/27590858/usp7-promotes-cell-proliferation-through-the-stabilization-of-ki-67-protein-in-non-small-cell-lung-cancer-cells
#20
Chao Zhang, Jing Lu, Quan-Wu Zhang, Wei Zhao, Jia-Hui Guo, Shan-Ling Liu, Ying-Li Wu, Bin Jiang, Feng-Hou Gao
The Ki-67 antigen (Ki-67) is the most reliable immunohistochemical marker for evaluation of cell proliferation in non-small cell lung cancer. However, the mechanisms underlying the regulation of protein levels of Ki-67 in non-small cell lung cancer have remained elusive. In this study, we found that Ki-67 and ubiquitin-specific processing protease 7 (USP7) protein were highly expressed in the nucleus of non-small cell lung cancer cells. Furthermore, statistical analysis uncovered the existence of a strong correlation between Ki-67 and USP7 levels...
October 2016: International Journal of Biochemistry & Cell Biology
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