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https://www.readbyqxmd.com/read/29899379/a-complex-of-the-ubiquitin-ligase-trim32-and-the-deubiquitinase-usp7-balances-the-level-of-c-myc-ubiquitination-and-thereby-determines-neural-stem-cell-fate-specification
#1
Sarah Nicklas, Anna-Lena Hillje, Satoshi Okawa, Ina-Maria Rudolph, Franziska Melanie Collmann, Thea van Wuellen, Antonio Del Sol, Jens C Schwamborn
The balance between stem cell maintenance and differentiation has been proposed to depend on antagonizing ubiquitination and deubiquitination reactions of key stem cell transcription factors (SCTFs) mediated by pairs of E3 ubiquitin ligases and deubiquitinating enzymes. Accordingly, increased ubiquitination results in proteasomal degradation of the SCTF, thereby inducing cellular differentiation, whereas increased deubiquitination stabilizes the SCTF, leading to maintenance of the stem cell fate. In neural stem cells, one of the key SCTFs is c-Myc...
June 13, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29863498/destabilizing-nek2-overcomes-resistance-to-proteasome-inhibition-in-multiple-myeloma
#2
Reinaldo Franqui-Machin, Mu Hao, Hua Bai, Zhimin Gu, Xin Zhan, Hasem Habelhah, Yogesh Jethava, Lugui Qiu, Ivana Frech, Guido Tricot, Fenghuang Zhan
Drug resistance remains the key problem in cancer treatment. It is now accepted that each myeloma patient harbors multiple subclones and subclone dominance may change over time. The coexistence of multiple subclones with high or low chromosomal instability (CIN) signature causes heterogeneity and drug resistance with consequent disease relapse. In this study, using a tandem affinity purification-mass spectrometry (TAP-MS) technique, we found that NEK2, a CIN gene, was bound to the deubiquitinase USP7. Binding to USP7 prevented NEK2 ubiquitination resulting in NEK2 stabilization...
June 4, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29795372/fam188b-enhances-cell-survival-via-interaction-with-usp7
#3
Eun-Seok Choi, Hanna Lee, Jee Young Sung, Chang-Hun Lee, Hyonchol Jang, Kyung Tae Kim, Yong-Nyun Kim, Hyoung-Pyo Kim, Sung-Ho Goh
We have previously reported that FAM188B showed significant differential exon usage in cancers (NCBI GEO GSE30727), but the expression and function of FAM188B is not well characterized. In the present study, we explored the functions of FAM188B by a knockdown strategy, using siRNAs specific for FAM188B in colon cancer cell lines. FAM188B is a novel gene that encodes a protein that is evolutionarily conserved among mammals. Its mRNA has been found to be highly expressed in most solid tumors, including colorectal cancer...
May 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29781103/targeting-ubiquitin-specific-protease-7-in-cancer-a-deubiquitinase-with-great-prospects
#4
REVIEW
Farjana Yeasmin Khusbu, Fang-Zhi Chen, Han-Chun Chen
Deubiquitinase (DUB)-mediated cleavage of ubiquitin chain balances ubiquitination and deubiquitination for determining protein fate. USP7 is one of the best characterized DUBs and functionally important. Numerous proteins have been identified as potential substrates and binding partners of USP7; those play crucial roles in diverse array of cellular and biological processes including tumour suppression, cell cycle, DNA repair, chromatin remodelling, and epigenetic regulation. This review aims at summarizing the current knowledge of this wide association of USP7 with many cellular processes that enlightens the possibility of abnormal USP7 activity in promoting oncogenesis and the importance of identification of specific inhibitors...
May 20, 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29748603/tspy1-suppresses-usp7-mediated-p53-function-and-promotes-spermatogonial-proliferation
#5
Ying Shen, Wenling Tu, Yunqiang Liu, Xiling Yang, Qiang Dong, Bo Yang, Jinyan Xu, Yuanlong Yan, Xue Pei, Mohan Liu, Wenming Xu, Yuan Yang
Testis-specific protein Y-linked 1 (TSPY1) is expressed predominantly in adult human spermatogonia and functions in the process of spermatogenesis; however, our understanding of the underlying mechanism is limited. Here we observed that TSPY1, as an interacting partner of TSPY-like 5 (TSPYL5), enhanced the competitive binding of TSPYL5 to ubiquitin-specific peptidase 7 (USP7) in conjunction with p53. This activity, together with its promotion of TSPYL5 expression by acting as a transcription factor, resulted in increased p53 ubiquitylation...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29688809/usp7-trim27-axis-negatively-modulates-antiviral-type-i-ifn-signaling
#6
Juan Cai, Hong-Yan Chen, Shu-Jie Peng, Jun-Ling Meng, Yan Wang, Yu Zhou, Xiao-Ping Qian, Xiu-Yuan Sun, Xue-Wen Pang, Yu Zhang, Jun Zhang
Ubiquitination and deubiquitination are important post-translational regulatory mechanisms responsible for fine tuning the antiviral signaling. In this study, we identified a deubiquitinase, the ubiquitin-specific peptidase 7/herpes virus associated ubiquitin-specific protease (USP7/HAUSP) as an important negative modulator of virus-induced signaling. Overexpression of USP7 suppressed Sendai virus and polyinosinic-polycytidylic acid and poly(deoxyadenylic-deoxythymidylic)-induced ISRE and IFN-β activation, and enhanced virus replication...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29616860/targeting-hausp-in-both-p53-wildtype-and-p53-mutant-tumors
#7
Omid Tavana, Hongbin Sun, Wei Gu
Inhibition of Mdm2 function is a validated approach to restore p53 activity for cancer therapy; nevertheless, inhibitors of Mdm2 such as Nutlin-3 have certain limitations, suggesting that additional targets in this pathway need to be further elucidated. Our finding that the Herpesvirus-Associated Ubiquitin-Specific Protease (HAUSP, also called USP7) interacts with the p53/Mdm2 protein complex, was one of the first examples that deubiquitinases (DUBs) exhibit a specific role in regulating protein stability. Here, we show that inhibitors of HAUSP and Nutlin-3 can synergistically activate p53 function and induce p53-dependent apoptosis in human cancer cells...
May 15, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29581288/small-proline-rich-protein-2b-drives-stress-dependent-p53-degradation-and-fibroblast-proliferation-in-heart-failure
#8
Ryan M Burke, Janet K Lighthouse, Pearl Quijada, Ronald A Dirkx, Alexander Rosenberg, Christine S Moravec, Jeffrey D Alexis, Eric M Small
Heart disease is associated with the accumulation of resident cardiac fibroblasts (CFs) that secrete extracellular matrix (ECM), leading to the development of pathological fibrosis and heart failure. However, the mechanisms underlying resident CF proliferation remain poorly defined. Here, we report that small proline-rich protein 2b ( Sprr2b ) is among the most up-regulated genes in CFs during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the USP7/MDM2-containing ubiquitination complex...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29574466/clinical-significance-of-ubiquitin-specific-protease-7-usp7-in-predicting-prognosis-of-hepatocellular-carcinoma-and-its-functional-mechanisms
#9
Xujing Wang, Qiqi Zhang, Yongkun Wang, Huiren Zhuang, Bo Chen
BACKGROUND Hepatocellular carcinoma (HCC) accounts for one of the most prevalent cancer types in the world. The ubiquitin specific protease 7 (USP7), a kind of deubiquitylating enzyme, has been reported to play multifaceted roles in different tumor types. The aim of this study was to investigate the expression and function of USP7 in HCC. MATERIAL AND METHODS Immunohistochemical staining and quantitative PCR were performed to explore the expression of USP7 in both HCC tissues and adjacent normal liver tissues...
March 25, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29557344/retreatment-with-sofosbuvir-velpatasvir-in-cirrhotic-patients-with-genotype-4-who-failed-a-previous-interferon-free-regimen-a-case-series
#10
Lucio Boglione, Simone Mornese Pinna, Tommaso Lupia, Giuseppe Cariti, Giovanni Di Perri
BACKGROUND: The novel available interferon (IFN)-free regimens significantly improved the sustained virological response (SVR) in patients with chronic hepatitis C (CHC), without important side effects and with shorter duration of treatment. In a subset of patients, however, the treatment failure (TF) was due to the presence of resistance-associated substitutions (RAS) that lead to virological breakthrough (BT) or relapse. We analysed in this case series the role of RAS on the TF in cirrhotic patients with genotype (GT)4, treated with a previous IFN-free regimen, and retreated with the combination of sofosbuvir (SOF)/velpatasvir (VEL) for 12 or 24 weeks, without ribavirin (RBV)...
February 14, 2018: Antiviral Therapy
https://www.readbyqxmd.com/read/29541367/identification-and-structure-guided-development-of-pyrimidinone-based-usp7-inhibitors
#11
Colin R O'Dowd, Matthew D Helm, J S Shane Rountree, Jakub T Flasz, Elias Arkoudis, Hugues Miel, Peter R Hewitt, Linda Jordan, Oliver Barker, Caroline Hughes, Ewelina Rozycka, Eamon Cassidy, Keeva McClelland, Ewa Odrzywol, Natalie Page, Stephanie Feutren-Burton, Scarlett Dvorkin, Gerald Gavory, Timothy Harrison
Ubiquitin specific protease 7 (USP7, HAUSP) has become an attractive target in drug discovery due to the role it plays in modulating Mdm2 levels and consequently p53. Increasing interest in USP7 is emerging due to its potential involvement in oncogenic pathways as well as possible roles in both metabolic and immune disorders in addition to viral infections. Potent, novel, and selective inhibitors of USP7 have been developed using both rational and structure-guided design enabled by high-resolution cocrystallography...
March 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29507645/overexpression-of-uhrf1-promotes-silencing-of-tumor-suppressor-genes-and-predicts-outcome-in-hepatoblastoma
#12
Alexander Beck, Franziska Trippel, Alexandra Wagner, Saskia Joppien, Max Felle, Christian Vokuhl, Thomas Schwarzmayr, Tim M Strom, Dietrich von Schweinitz, Gernot Längst, Roland Kappler
Background: Hepatoblastoma (HB) is the most common liver tumor of childhood and occurs predominantly within the first 3 years of life. In accordance to its early manifestation, HB has been described to display an extremely low mutation rate. As substitute, epigenetic modifiers seem to play an exceptional role in its tumorigenesis, which holds promise to develop targeted therapies and establish biomarkers for patient risk stratification. Results: We examined the role of a newly described protein complex consisting of three epigenetic regulators, namely E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), ubiquitin-specific-processing protease 7 (USP7), and DNA methyltransferase 1 (DNMT1), in HB...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29482658/independent-functions-of-dnmt1-and-usp7-at-replication-foci
#13
Olya Yarychkivska, Omid Tavana, Wei Gu, Timothy H Bestor
BACKGROUND: It has been reported that USP7 (ubiquitin-specific protease 7) prevents ubiquitylation and degradation of DNA methyltransferase 1 (DNMT1) by direct binding of USP7 to the glycine-lysine (GK) repeats that join the N-terminal regulatory domain of DNMT1 to the C-terminal methyltransferase domain. The USP7-DNMT1 interaction was reported to be mediated by acetylation of lysine residues within the (GK) repeats. RESULTS: We found that DNMT1 is present at normal levels in mouse and human cells that contain undetectable levels of USP7...
February 27, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29478093/new-geranyl-flavonoids-from-the-leaves-of-artocarpus-communis
#14
Masamitsu Inoue, Yuki Hitora, Hikaru Kato, Fitje Losung, Remy E P Mangindaan, Sachiko Tsukamoto
Four new geranyl flavonoids 1-4 and four known flavonoids 5-8 were obtained from the leaves of Artocarpus communis collected in Indonesia. The planar structures of flavonoids were elucidated by analyses of MS and NMR spectroscopic data. Absolute configurations of 1 and 2 were determined by ECD spectroscopy. Analyses by HPLC with a chiral-phase column and ECD spectra confirmed that 3 and 4 were stereoisomeric mixtures and 7 and 8 were racemic mixtures. The compounds obtained in this study inhibited the enzymatic activities of ubiquitin-specific protease 7 (USP7) and the chymotrypsin-like activity of the proteasome...
February 24, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29416040/bre-brcc45-regulates-cdc25a-stability-by-recruiting-usp7-in-response-to-dna-damage
#15
Kajal Biswas, Subha Philip, Aditya Yadav, Betty K Martin, Sandra Burkett, Vaibhav Singh, Anav Babbar, Susan Lynn North, Suhwan Chang, Shyam K Sharan
BRCA2 is essential for maintaining genomic integrity. BRCA2-deficient primary cells are either not viable or exhibit severe proliferation defects. Yet, BRCA2 deficiency contributes to tumorigenesis. It is believed that mutations in genes such as TRP53 allow BRCA2 heterozygous cells to overcome growth arrest when they undergo loss of heterozygosity. Here, we report the use of an insertional mutagenesis screen to identify a role for BRE (Brain and Reproductive organ Expressed, also known as BRCC45), known to be a part of the BRCA1-DNA damage sensing complex, in the survival of BRCA2-deficient mouse ES cells...
February 7, 2018: Nature Communications
https://www.readbyqxmd.com/read/29395786/an-intramolecular-interaction-of-uhrf1-reveals-dual-control-for-its-histone-association
#16
Linfeng Gao, Xiao-Feng Tan, Shen Zhang, Tianchen Wu, Zhi-Min Zhang, Hui-Wang Ai, Jikui Song
UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) is one of the essential components of mammalian DNA methylation machinery. Chromatin association of UHRF1 is controlled via an interplay between its intramolecular interaction and dual recognition of histone H3 trimethylated at lysine 9 (H3K9me3) and hemimethylated DNA. Here, we report the crystal structure of the N-terminal tandem Tudor domain (TTD) of UHRF1 in complex with the C-terminal polybasic region (PBR). Structural analysis reveals that PBR binding leads to displacement of the TTD-plant homeodomain (PHD) linker, as well as blockage of the H3K9me3-engaging cage, both of which contribute to a chromatin-occluded UHRF1 conformation...
February 6, 2018: Structure
https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#17
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract, and an impaired immune response plays a critical role in IBD. The current drugs and therapies for IBD treatment are of limited use, therefore, there is a need to find novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via a Treg-cell-mediated effect on the immune response...
April 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29343584/human-herpesvirus-8-interferon-regulatory-factors-1-and-3-mediate-replication-and-latency-activities-via-interactions-with-usp7-deubiquitinase
#18
Qiwang Xiang, Hyunwoo Ju, Qian Li, Szu-Chieh Mei, Daming Chen, Young Bong Choi, John Nicholas
Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors (vIRF-1 to -4) that likely function to suppress innate immune and cellular stress responses through inhibitory interactions with various cellular proteins involved in these activities. It is notable that vIRF-1 and -4 have been reported to interact with the deubiquitinase ubiquitin-specific protease 7 (USP7), substrates of which include p53 and the p53-targeting and -destabilizing ubiquitin E3 ligase MDM2. Structural studies of vIRF-1 and vIRF-4 USP7 binding sequences in association with USP7 have been reported; both involve interactions with N-terminal-domain residues of USP7 via EGPS and ASTS motifs in vIRF-1 and vIRF-4, respectively, but vIRF-4 residues also contact the catalytic site...
April 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29337966/drug-development-allosteric-inhibitors-hit-usp7-hard
#19
Wei Zhang, Sachdev S Sidhu
No abstract text is available yet for this article.
January 16, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29323787/inhibition-of-uvssa-ubiquitination-suppresses-transcription-coupled-nucleotide-excision-repair-deficiency-caused-by-dissociation-from-usp7
#20
Mitsuru Higa, Kiyoji Tanaka, Masafumi Saijo
Transcription-coupled nucleotide excision repair (TC-NER) is a subpathway of nucleotide excision repair that efficiently removes transcription-blocking DNA damage from the transcribed strands of active genes. UVSSA is a causative gene for UV-sensitive syndrome (UVS S), which is an autosomal recessive disorder characterized by hypersensitivity to UV light and deficiency in TC-NER. UV-stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with ubiquitin-specific peptidase 7 (USP7) and is stabilized by interaction with USP7...
March 2018: FEBS Journal
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