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Ubiquitin-specific protease

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https://www.readbyqxmd.com/read/27904772/mir-101-targets-usp22-to-inhibit-the-tumorigenesis-of-papillary-thyroid-carcinoma
#1
Huadong Zhao, Haili Tang, Qike Huang, Bo Qiu, Xiaomin Liu, Dong Fan, Li Gong, Hang Guo, Chong Chen, Shixiong Lei, Lu Yang, Jianguo Lu, Guoqiang Bao
Increasing evidence suggests that microRNA-101 (miR-101) is involved in the progression of various human cancers, including papillary thyroid carcinoma (PTC). However, the biological functions of miR-101 and underlying molecular mechanisms in PTC remain largely unknown. In this study, we demonstrated that miR-101 underexpression in PTC tissue was associated with lymph node metastasis and poor prognosis of PTC patients. MiR-101 reduced PTC cell proliferation, apoptosis resistance, and invasion. Ubiquitin-specific protease 22 (USP22) was confirmed as a direct target of miR-101...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27899971/the-targetable-role-of-herpes-virus-associated-ubiquitin-specific-protease-hausp-in-p190-bcr-abl-leukemia
#2
Giovanna Carrà, Cristina Panuzzo, Sabrina Crivellaro, Deborah Morena, Riccardo Taulli, Angelo Guerrasio, Giuseppe Saglio, Alessandro Morotti
Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) is driven by the p190 breakpoint cluster region (BCR)-ABL isoform. Although effectively targeted by BCR-ABL tyrosine kinase inhibitors (TKIs), ALL is associated with a less effective response to TKIs compared with chronic myeloid leukemia. Therefore, the identification of additional genes required for ALL maintenance may provide possible therapeutic targets to aid the eradication of this cancer. The present study demonstrated that p190 BCR-ABL is able to interact with the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP), which in turn affects p53 protein stability...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#3
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27871365/mechanism-and-regulation-of-dna-protein-crosslink-repair-by-the-dna-dependent-metalloprotease-sprtn
#4
Julian Stingele, Roberto Bellelli, Ferdinand Alte, Graeme Hewitt, Grzegorz Sarek, Sarah L Maslen, Susan E Tsutakawa, Annabel Borg, Svend Kjær, John A Tainer, J Mark Skehel, Michael Groll, Simon J Boulton
Covalent DNA-protein crosslinks (DPCs) are toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription. Little was known about DPC-specific repair mechanisms until the recent identification of a DPC-processing protease in yeast. The existence of a DPC protease in higher eukaryotes is inferred from data in Xenopus laevis egg extracts, but its identity remains elusive. Here we identify the metalloprotease SPRTN as the DPC protease acting in metazoans. Loss of SPRTN results in failure to repair DPCs and hypersensitivity to DPC-inducing agents...
November 17, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27852060/senp1-regulates-pten-stability-to-dictate-prostate-cancer-development
#5
Tasneem Bawa-Khalfe, Feng-Ming Yang, Joan Ritho, Hui-Kuan Lin, Jinke Cheng, Edward T H Yeh
SUMO protease SENP1 is elevated in multiple carcinomas including prostate cancer (PCa). SENP1 exhibits carcinogenic properties; it promotes androgen receptor-dependent and -independent cell proliferation, stabilizes HIF1α, increases VEGF, and supports angiogenesis. However, mice expressing an androgen-responsive promoter driven SENP1-transgene (SENP1-Tg) develop high-grade prostatic intraepithelial neoplasia, but not carcinoma. We now show that tumor suppressive PTEN signaling is induced in SENP1-Tg to enhance prostate epithelial cell apoptosis...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27831570/a-cell-free-organelle-based-in-vitro-system-for-studying-the-peroxisomal-protein-import-machinery
#6
Tony A Rodrigues, Tânia Francisco, Ana F Dias, Ana G Pedrosa, Cláudia P Grou, Jorge E Azevedo
Here we describe a protocol to dissect the peroxisomal matrix protein import pathway using a cell-free in vitro system. The system relies on a postnuclear supernatant (PNS), which is prepared from rat/mouse liver, to act as a source of peroxisomes and cytosolic components. A typical in vitro assay comprises the following steps: (i) incubation of the PNS with an in vitro-synthesized (35)S-labeled reporter protein; (ii) treatment of the organelle suspension with a protease that degrades reporter proteins that have not associated with peroxisomes; and (iii) SDS-PAGE/autoradiography analysis...
December 2016: Nature Protocols
https://www.readbyqxmd.com/read/27830160/usp9x-deletion-elevates-the-density-of-oligodendrocytes-within-the-postnatal-dentate-gyrus
#7
Sabrina Oishi, Oressia Zalucki, Susitha Premarathne, Stephen A Wood, Michael Piper
Neural stem cells (NSCs) within the adult hippocampal dentate gyrus reside in the subgranular zone (SGZ). A dynamic network of signaling mechanisms controls the balance between the maintenance of NSC identity, and their subsequent differentiation into dentate granule neurons. Recently, the ubiquitin-specific protease 9 X-linked (USP9X) was shown to be important for hippocampal morphogenesis, as mice lacking this gene exhibited a higher proportion of proliferating NSCs, yet a decrease in neuronal numbers, within the postnatal dentate gyrus...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27824081/the-nucleolar-protein-gltscr2-is-required-for-efficient-viral-replication
#8
Peng Wang, Wen Meng, Shi-Chong Han, Cui-Cui Li, Xiao-Jun Wang, Xiao-Jia Wang
Glioma tumor suppressor candidate region gene 2 protein (GLTSCR2) is a nucleolar protein. In the investigation of the role of GLTSCR2 that played in the cellular innate immune response to viral infection, we found GLTSCR2 supported viral replication of rhabdovirus, paramyxovirus, and coronavirus in cells. Viral infection induced translocation of GLTSCR2 from nucleus to cytoplasm that enabled GLTSCR2 to attenuate type I interferon IFN-β and support viral replication. Cytoplasmic GLTSCR2 was able to interact with retinoic acid-inducible gene I (RIG-I) and the ubiquitin-specific protease 15 (USP15), and the triple interaction induced USP15 activity to remove K63-linked ubiquitination of RIG-I, leading to attenuation of RIG-I and IFN-β...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27813535/coinhibition-of-the-deubiquitinating-enzymes-usp14-and-uchl5-with-vlx1570-is-lethal-to-ibrutinib-or-bortezomib-resistant-waldenstrom-macroglobulinemia-tumor-cells
#9
A Paulus, S Akhtar, T R Caulfield, K Samuel, H Yousaf, Y Bashir, S M Paulus, D Tran, R Hudec, D Cogen, J Jiang, B Edenfield, A Novak, S M Ansell, T Witzig, P Martin, M Coleman, V Roy, S Ailawadhi, K Chitta, S Linder, A Chanan-Khan
The survival of Waldenstrom macroglobulinemia (WM) tumor cells hinges on aberrant B-cell receptor (BCR) and MYD88 signaling. WM cells upregulate the proteasome function to sustain the BCR-driven growth while maintaining homeostasis. Clinically, two treatment strategies are used to disrupt these complementary yet mutually exclusive WM survival pathways via ibrutinib (targets BTK/MYD88 node) and bortezomib (targets 20 S proteasome). Despite the success of both agents, WM patients eventually become refractory to treatment, highlighting the adaptive plasticity of WM cells and underscoring the need for development of new therapeutics...
November 4, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27810359/the-testis-specific-usp26-is-a-deubiquitinating-enzyme-of-the-ubiquitin-ligase-mdm2
#10
Shirly Lahav-Baratz, Yelena Kravtsova-Ivantsiv, Shai Golan, Aaron Ciechanover
Murine double minute-2 (Mdm2) is one of the E3-ligases of the androgen receptor besides being the major regulator of the p53 tumor suppressor. The testis-specific USP26 was demonstrated to regulate the androgen receptor. In the present study we examined possible association between the deubiquitinating enzyme - ubiquitin specific protease 26 (USP26), and the oncoprotein E3 ligase - (Mdm-2). We analyzed the half-life time of USP26 in HEK293 cells. In a cell-free system we asked whether USP26 can be ubiquitinated by HeLa extract...
October 31, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27779380/quantitative-chemical-proteomic-profiling-of-ubiquitin-specific-proteases-in-intact-cancer-cells
#11
Jennifer A Ward, Lauren McLellan, Martin Stockley, Karl R Gibson, Gavin A Whitlock, Charlotte Knights, Jeanine A Harrigan, Xavier Jacq, Edward W Tate
Deubiquitinating enzymes play an important role in a plethora of therapeutically relevant processes and are emerging as pioneering drug targets. Herein, we present a novel probe, Ubiquitin Specific Protease (USP) inhibitor, alongside an alkyne-tagged activity-based probe analogue. Activity-based proteome profiling identified 12 USPs, including USP4, USP16, and USP33, as inhibitor targets using submicromolar probe concentrations. This represents the first intact cell activity-based profiling of deubiquitinating enzymes...
October 31, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27776223/the-substrate-binding-domains-of-human-siah-e3-ubiquitin-ligases-are-now-crystal-clear
#12
Qi Zhang, Zhongduo Wang, Feng Hou, Rachel Harding, Xinyi Huang, Aiping Dong, John R Walker, Yufeng Tong
BACKGROUND: Seven in absentia homologs (SIAHs) comprise a family of highly conserved E3 ubiquitin ligases that play an important role in regulating signalling pathways in tumorigenesis, including the DNA damage repair and hypoxia response pathways. SIAH1 and SIAH2 have been found to function as a tumour repressor and a proto-oncogene, respectively, despite the high sequence identity of their substrate binding domains (SBDs). Ubiquitin-specific protease USP19 is a deubiquitinase that forms a complex with SIAHs and counteracts the ligase function...
October 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#13
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...
October 15, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27769071/the-deubiquitinase-usp54-is-overexpressed-in-colorectal-cancer-stem-cells-and-promotes-intestinal-tumorigenesis
#14
Julia M Fraile, Diana Campos-Iglesias, Francisco Rodríguez, Yaiza Español, José M P Freije
Ubiquitin-Specific Proteases (USPs) are deubiquitinating enzymes frequently deregulated in human malignancies. Here, we show that USP54 is overexpressed in intestinal stem cells and demonstrate that its downregulation in colorectal carcinoma cells impedes tumorigenesis. We have generated mutant mice deficient for this deubiquitinase, which are viable and fertile, and protected against chemically-induced colorectal carcinoma. Furthermore, we show that USP54 is upregulated in human colon cancer and associates with poor prognosis...
October 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27761651/sumo-proteases-ots1-and-2-control-filament-elongation-through-a-della-dependent-mechanism
#15
Alberto Campanaro, Raffaella Battaglia, Massimo Galbiati, Ari Sadanandom, Chiara Tonelli, Lucio Conti
SUMOylation and anther growth. During fertilization, stamen elongation needs to be synchronized with pistil growth. The phytohormone gibberellic acid (GA) promotes stamen growth by stimulating the degradation of growth repressing DELLA proteins. DELLA accumulation is negatively regulated by GAs through the ubiquitin-proteasome system. In Arabidopsis thaliana, a proportion of DELLAs is also conjugated to the small ubiquitin-like modifier (SUMO) protein, which stabilizes DELLAs. Increased DELLA levels occur in the SUMO protease-deficient OVERLY TOLERANT TO SALT 1 and 2 (ots1 ots2) double mutants, especially under salt stress conditions...
December 2016: Plant Reproduction
https://www.readbyqxmd.com/read/27761137/selection-of-reliable-reference-genes-for-gene-expression-analysis-under-abiotic-stresses-in-the-desert-biomass-willow-salix-psammophila
#16
Jianbo Li, Huixia Jia, Xiaojiao Han, Jin Zhang, Pei Sun, Mengzhu Lu, Jianjun Hu
Salix psammophila is a desert shrub willow that has extraordinary adaptation to abiotic stresses and plays an important role in maintaining local ecosystems. Moreover, S. psammophila is regarded as a promising biomass feedstock because of its high biomass yields and short rotation coppice cycle. However, few suitable reference genes (RGs) for quantitative real-time polymerase chain reaction (qRT-PCR) constrain the study on normalization of gene expression in S. psammophila until now. Here, we investigated the expression stabilities of 14 candidate RGs across tissue types and under four abiotic stress treatments, including heat, cold, salt, and drought treatments...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27756680/steady-state-kinetic-studies-reveal-that-the-anti-cancer-target-ubiquitin-specific-protease-17-usp17-is-a-highly-efficient-deubiquitinating-enzyme
#17
Nicole M Hjortland, Andrew D Mesecar
USP17 is a deubiquitinating enzyme that is upregulated in numerous cancers and therefore a drug target. We developed a robust expression, purification, and assay system for USP17 enabling its enzymatic and structural characterization. USP17 was expressed in E. coli as inclusion bodies and then solubilized, refolded, and purified using affinity and size-exclusion chromatography. Milligram quantities of pure USP17 can be produced that is catalytically more efficient (kcat/Km = 1500 (x10(3)) M(-1)sec(-1)) than other human USPs studied to date...
October 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27726449/single-nucleotide-polymorphisms-of-usp26-in-azoospermic-men
#18
Alice Luddi, Laura Crifasi, Antonella Quagliarello, Laura Governini, Vincenzo De Leo, Paola Piomboni
Some studies have focused on the association between male infertility and single nucleotide polymorphisms (SNPs) in the ubiquitin-specific protease 26 (USP26) gene, but the results are controversial. In this case-control study including both normozoospermic men and patients with nonobstructive azoospermia, we analyzed both the entire coding region and 5' and 3' untranslated regions of USP26 in order to identify genetic variants in this gene to investigate the role of USP26 on spermatogenesis. We reported variations in the USP26 gene sequence in 82% of azoospermic and in 50% normospermic men...
October 11, 2016: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/27723317/selenocysteine-as-a-latent-bioorthogonal-electrophilic-probe-for-deubiquitylating-enzymes
#19
Samuel D Whedon, Nagula Markandeya, Ambar S J B Rana, Caroline E Weller, Nicholas A Senger, Frantisek Turecek, Eric R Strieter, Champak Chatterjee
Deubiquitylating enzymes (DUBs) remove ubiquitin (Ub) from various cellular proteins and render eukaryotic ubiquitylation a dynamic process. The misregulation of protein ubiquitylation is associated with many human diseases, and there is an urgent need to identify specific DUBs associated with therapeutically relevant targets of Ub. We report the development of two facile selenocysteine-based strategies to generate the DUB probe dehydroalanine (Dha). Optimized oxidative or alkylative elimination of Se yielded Dha at the C-terminus of Ub...
October 10, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27716962/acetaldehyde-disrupts-interferon-alpha-signaling-in-hepatitis-c-virus-infected-liver-cells-by-up-regulating-usp18
#20
Murali Ganesan, Larisa Y Poluektova, Dean J Tuma, Kusum K Kharbanda, Natalia A Osna
BACKGROUND: Alcohol consumption exacerbates the pathogenesis of hepatitis C virus (HCV) infection and worsens disease outcomes. The exact reasons are not clear yet, but they might be partially attributed to the ability of alcohol to further suppress the innate immunity. Innate immunity is known to be already decreased by HCV in liver cells. METHODS: In this study, we aimed to explore the mechanisms of how alcohol metabolism dysregulates IFNα signaling (STAT1 phosphorylation) in HCV(+) hepatoma cells...
September 26, 2016: Alcoholism, Clinical and Experimental Research
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