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https://www.readbyqxmd.com/read/27915049/csn1201-a-subunit-of-the-cop9-signalosome-regulates-the-virulence-in-cryptococcus-neoformans-infection
#1
Yibin Fan, Xiaohua Tao, Weili Pan, Wei Fang, Youming Huang, Mingyan Jia
The COP9 signalosome (CSN) is a multisubunit protein complex, and it now has been found to participate in diverse cellular and developmental processes in various eukaryotic organisms. Cryptococcus neoformans (C. neoformans) is an important basidiomycete pathogen that causes life-threatening meningoencephalitis primarily in the immune compromised population. Here, we generated CSN deletion mutants to investigate the role in Cryptococcus infection. Compared to other CSN mutants, we identified a CSN1201 mutant exhibited severely attenuated virulence...
November 30, 2016: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/27903243/analysis-of-rna-expression-of-normal-and-cancer-tissues-reveals-high-correlation-of-cop9-gene-expression-with-respiratory-chain-complex-components
#2
Christina A Wicker, Tadahide Izumi
BACKGROUND: The COP9 signalosome, composed of eight subunits, is implicated in cancer genetics with its deneddylase activity to modulate cellular concentration of oncogenic proteins such as IkB and TGFβ. However, its function in the normal cell physiology remains elusive. Primarily focusing on gene expression data of the normal tissues of the head and neck, the cancer genome atlas (TCGA) database was used to identify groups of genes that were expressed synergistically with the COP9 genes, particularly with the COPS5 (CSN5), which possesses the catalytic activity of COP9...
December 1, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27869306/roles-of-multifunctional-cop9-signalosome-complex-in-cell-fate-and-implications-for-drug-discovery
#3
REVIEW
Ping Li, Longxiang Xie, Yinzhong Gu, Jiang Li, Jianping Xie
The eight subunits containing COP9 signalosome (CSN) complex, is highly conserved among eukaryotes. CSN, identified as a negative regulator of photomorphogenesis, has also been demonstrated to be important in proteolysis, cellular signal transduction and cell cycle regulation in various eukaryotic organisms. This review mainly summarizes the roles of CSN in cell cycle regulation, signal transduction and apoptosis, and its potential as diagnostic biomarkers, drug targets for cancer and infectious diseases. This article is protected by copyright...
November 21, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27866850/deubiquitination-and-stabilization-of-pd-l1-by-csn5
#4
Seung-Oe Lim, Chia-Wei Li, Weiya Xia, Jong-Ho Cha, Li-Chuan Chan, Yun Wu, Shih-Shin Chang, Wan-Chi Lin, Jung-Mao Hsu, Yi-Hsin Hsu, Taewan Kim, Wei-Chao Chang, Jennifer L Hsu, Hirohito Yamaguchi, Qingqing Ding, Yan Wang, Yi Yang, Chung-Hsuan Chen, Aysegul A Sahin, Dihua Yu, Gabriel N Hortobagyi, Mien-Chie Hung
Pro-inflammatory cytokines produced in the tumor microenvironment lead to eradication of anti-tumor immunity and enhanced tumor cell survival. In the current study, we identified tumor necrosis factor alpha (TNF-α) as a major factor triggering cancer cell immunosuppression against T cell surveillance via stabilization of programmed cell death-ligand 1 (PD-L1). We demonstrated that COP9 signalosome 5 (CSN5), induced by NF-κB p65, is required for TNF-α-mediated PD-L1 stabilization in cancer cells. CSN5 inhibits the ubiquitination and degradation of PD-L1...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27833851/overexpression-of-cop9-signalosome-subunits-csn7a-and-csn7b-exerts-different-effects-on-adipogenic-differentiation
#5
Xiaohua Huang, Jürgen Ordemann, Johann Pratschke, Wolfgang Dubiel
The COP9 signalosome (CSN) is an essential regulator of cullin-RING-ubiquitin (Ub) ligases (CRLs), which ubiquitinate important cellular regulators and target them for degradation by the Ub proteasome system (UPS). The CSN exhibits deneddylating activity localized on subunit CSN5, which removes the ubiquitin-like protein Nedd8 from the cullins of CRLs. CSN-mediated deneddylation is an important step in the process of CRL remodeling, in which new substrate recognition units are incorporated into Ub ligases to meet changed requirements for proteolysis in cells...
November 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27774986/targeted-inhibition-of-the-cop9-signalosome-for-treatment-of-cancer
#6
Anita Schlierf, Eva Altmann, Jean Quancard, Anne B Jefferson, René Assenberg, Martin Renatus, Matthew Jones, Ulrich Hassiepen, Michael Schaefer, Michael Kiffe, Andreas Weiss, Christian Wiesmann, Richard Sedrani, Jörg Eder, Bruno Martoglio
The COP9 signalosome (CSN) is a central component of the activation and remodelling cycle of cullin-RING E3 ubiquitin ligases (CRLs), the largest enzyme family of the ubiquitin-proteasome system in humans. CRLs are implicated in the regulation of numerous cellular processes, including cell cycle progression and apoptosis, and aberrant CRL activity is frequently associated with cancer. Remodelling of CRLs is initiated by CSN-catalysed cleavage of the ubiquitin-like activator NEDD8 from CRLs. Here we describe CSN5i-3, a potent, selective and orally available inhibitor of CSN5, the proteolytic subunit of CSN...
October 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27703676/associations-and-prognostic-significance-of-p27-kip1-jab1-and-skp2-in-non-hodgkin-lymphoma
#7
Yan Ma, Meijuan Yan, Hua Huang, Li Zhang, Qian Wang, Yaqi Zhao, Jianmei Zhao
Non-Hodgkin lymphoma (NHL) is a primary tumor arising in lymph nodes and lymphoid tissue. The incidence of NHL is increasing at an annual rate of 3%. The human Jun activation domain-binding protein 1/COP9 signalosome subunit 5 (Jab1/CSN5) is a negative regulator of the cell cycle inhibitor p27(Kip1) and abnormal expression of Jab1 is correlated with reduced p27 expression and associated with advanced tumor stage and poor prognosis in several human cancers. F-box protein S-phase kinase-interacting protein-2 (Skp2), the substrate recognition subunit of the Skp1-Cul1-F-box protein ubiquitin protein ligase complex, is required for the ubiquitination and consequent degradation of p27...
October 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27693579/the-oxoglutarate-receptor-1-oxgr1-modulates-pressure-overload-induced-cardiac-hypertrophy-in-mice
#8
Ameh Omede, Min Zi, Sukhpal Prehar, Arfa Maqsood, Nicholas Stafford, Mamas Mamas, Elizabeth Cartwright, Delvac Oceandy
The G-protein-coupled receptors (GPCRs) family of proteins play essential roles in the heart, including in the regulation of cardiac hypertrophy. One member of this family, the oxoglutarate receptor 1 (OXGR1), may have a crucial role in the heart because it acts as a receptor for α-ketoglutarate, a metabolite that is elevated in heart failure patients. OXGR1 is expressed in the heart but its precise function during cardiac pathophysiological process is unknown. Here we used both in vivo and in vitro approaches to investigate the role of OXGR1 in cardiac hypertrophy...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27640199/jab1-promotes-glioma-cell-proliferation-by-regulating-siah1-%C3%AE-catenin-pathway
#9
Yufu Zhu, Zhichao Qiu, Xiang Zhang, Fengyuan Qian, Bin Wang, Lei Wang, Hengliang Shi, Rutong Yu
Jab1 (Jun activation domain-binding protein 1), also known as CSN5 (COP9 signalosome subunit 5), is frequently overexpressed in several cancer types. However, the biological functions and the molecular mechanisms of the Jab1 protein in human gliomas have not been investigated. In this study, we found that Jab1 protein was increasingly expressed in human glioma tissues comparing with normal brain tissues (Non-tumor). This suggested that Jab1 might be involved in the development of glioma. Thus, the role of Jab1 in glioma cell proliferation was investigated using Jab1 loss- and gain-of-function...
September 17, 2016: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/27626169/the-putative-oncotarget-csn5-controls-a-transcription-uncorrelated-p53-mediated-autophagy-implicated-in-cancer-cell-survival-under-curcumin-treatment
#10
Qing-Yu Zhang, Rui Jin, Xian Zhang, Ji-Po Sheng, Fang Yu, Ren-Xiang Tan, Ying Pan, Jun-Jian Huang, Ling-Dong Kong
Curcumin has shown promise as a safe and specific anticancer agent. The COP9 signalosome (CSN) component CSN5, a known specific target for curcumin, can control p53 stability by increasing its degradation through ubiquitin system. But the correlation of CSN5-controlled p53 to anticancer therapeutic effect of curcumin is currently unknown. Here we showed that CSN5-controlled p53 was transcriptional inactive and responsible for autophagy in human normal BJ cells and cancer HepG2 cells under curcumin treatment...
September 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27613030/immunodepletion-and-immunopurification-as-approaches-for-csn-research
#11
Amnon Golan, Ning Wei, Elah Pick
The COP9 signalosome (CSN) is an evolutionary conserved complex that is found in all eukaryotes, and implicated in regulating the activity of Cullin-RING ubiquitin Ligases (CRLs). Activity of CRLs is highly regulated; complexes are active when the cullin subunit is covalently attached to the ubiquitin like modifier, Nedd8. Neddylation/deneddylation cycles are required for proper CRLs activity, and deneddylation is performed by the CSN complex.We describe here a method utilizing resin-coupled antibodies to deplete the CSN from human cell extracts, and to obtain endogenous CSN complexes by immunopurification...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27609838/emerging-roles-of-the-single-ef-hand-ca2-sensor-tescalcin-in-the-regulation-of-gene-expression-cell-growth-and-differentiation
#12
REVIEW
Ksenia G Kolobynina, Valeria V Solovyova, Konstantin Levay, Albert A Rizvanov, Vladlen Z Slepak
Tescalcin (TESC, also known as calcineurin-homologous protein 3, CHP3) is a 24-kDa EF-hand Ca(2+)-binding protein that has recently emerged as a regulator of cell differentiation and growth. The TESC gene has also been linked to human brain abnormalities, and high expression of tescalcin has been found in several cancers. The expression level of tescalcin changes dramatically during development and upon signal-induced cell differentiation. Recent studies have shown that tescalcin is not only subjected to up- or down-regulation, but also has an active role in pathways that drive cell growth and differentiation programs...
October 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27581057/a-wheat-cop9-subunit-5-like-gene-is-negatively-involved-in-host-response-to-leaf-rust
#13
Hongtao Zhang, Xiaojing Wang, Michael J Giroux, Li Huang
The COP9 (constitutive photomorphogenesis 9) signalosome (CSN) is a protein complex involved in the ubiquitin proteasome system and a common host target of diverse pathogens in Arabidopsis. The known derubylation function of the COP9 complex is carried out by subunit 5 encoded by AtCSN5A or AtCSN5B in Arabidopsis. A single CSN5-like gene (designated as TaCSN5) with three homeologues was identified on the long arms of wheat (Triticum aestivum L.) group 2 chromosomes. In this study, we identified and characterized the function of TaCSN5 in response to infection by the leaf rust pathogen...
August 31, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/27561782/d27e-mutation-of-vtc1-impairs-the-interaction-with-csn5b-and-enhances-ascorbic-acid-biosynthesis-and-seedling-growth-in-arabidopsis
#14
Shenghui Li, Juan Wang, Yanwen Yu, Fengru Wang, Jingao Dong, Rongfeng Huang
Our previous investigation revealed that GDP-Man pyrophosphorylase (VTC1), a vital ascorbic acid (AsA) biosynthesis enzyme, could be degraded through interaction with the photomorphogenic factor COP9 signalosome subunit 5B (CSN5B) in the darkness, demonstrating the posttranscriptional regulation of light signal in AsA production. Here, we further report that a point mutation in D27E of VTC1 disables the interaction with CSN5B, resulting in enhancement of AsA biosynthesis and seedling growth in Arabidopsis thaliana...
August 25, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27546621/csn6-controls-the-proliferation-and-metastasis-of-glioblastoma-by-chip-mediated-degradation-of-egfr
#15
J Hou, Q Deng, J Zhou, J Zou, Y Zhang, P Tan, W Zhang, H Cui
CSN6, a critical subunit of the constitutive photomorphogenesis 9 (COP9) signalosome (CSN), has received attention as a regulator of the degradation of cancer-related proteins such as p53, c-myc and c-Jun, through the ubiquitin-proteasome system, suggesting its importance in cancerogenesis. However, the biological functions and molecular mechanisms of CSN6 in glioblastoma (GBM) remain poorly understood. Here, we report that GBM tumors overexpressed CSN6 compared with normal brain tissues and that CSN6 promoted GBM cell proliferation, migration, invasion and tumorigenesis...
August 22, 2016: Oncogene
https://www.readbyqxmd.com/read/27423334/elucidation-of-the-genetic-basis-of-variation-for-stem-strength-characteristics-in-bread-wheat-by-associative-transcriptomics
#16
Charlotte N Miller, Andrea L Harper, Martin Trick, Peter Werner, Keith Waldron, Ian Bancroft
BACKGROUND: The current approach to reducing the tendency for wheat grown under high fertilizer conditions to collapse (lodge) under the weight of its grain is based on reducing stem height via the introduction of Rht genes. However, these reduce the yield of straw (itself an important commodity) and introduce other undesirable characteristics. Identification of alternative height-control loci is therefore of key interest. In addition, the improvement of stem mechanical strength provides a further way through which lodging can be reduced...
2016: BMC Genomics
https://www.readbyqxmd.com/read/27418125/signaling-pathways-regulating-cartilage-growth-plate-formation-and-activity
#17
William E Samsa, Xin Zhou, Guang Zhou
The growth plate is a highly specialized and dynamic cartilage structure that serves many essential functions in skeleton patterning, growth and endochondral ossification in developing vertebrates. Major signaling pathways initiated by classical morphogens and by other systemic and tissue-specific factors are intimately involved in key aspects of growth plate development. As a corollary of these essential functions, disturbances in these pathways due to mutations or environmental factors lead to severe skeleton disorders...
July 11, 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/27401219/transcriptome-meta-analysis-of-three-follicular-compartments-and-its-correlation-with-ovarian-follicle-maturity-and-oocyte-developmental-competence-in-cows
#18
Daulat Raheem Khan, David A Landry, Éric Fournier, Christian Vigneault, Patrick Blondin, Marc-André Sirard
Oocyte developmental competence in superstimulated cows is dependent in part on the duration of the FSH coasting. FSH coasting refers to superstimulation with FSH (2 days of endogenous FSH following follicle ablation and 3 days of FSH injections) followed by no FSH for a specific duration. The optimal duration varies among individuals. FSH coasting appears to modulate the transcriptome of different follicular compartments, which cooperate as a single functional unit. However, the integrative effects of FSH coasting on different follicular compartments remain ambiguous...
August 1, 2016: Physiological Genomics
https://www.readbyqxmd.com/read/27375289/cops5-amplification-and-overexpression-confers-tamoxifen-resistance-in-er%C3%AE-positive-breast-cancer-by-degradation-of-ncor
#19
Renquan Lu, Xiaobo Hu, Junmei Zhou, Jiajun Sun, Alan Z Zhu, Xiaofeng Xu, Hui Zheng, Xiang Gao, Xian Wang, Hongchuan Jin, Ping Zhu, Lin Guo
Oestrogen receptor α (ERα) antagonists are used in endocrine therapies for ERα-positive (ERα+) breast cancer patients. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. Here using integrated genomic and functional studies, we report that amplification and/or overexpression of COPS5 (CSN5/JAB1) confers resistance to tamoxifen. Amplification and overexpression of COPS5, a catalytic subunit of the COP9 complex, is present in about 9% of the ERα+ primary breast cancer and more frequently (86...
July 4, 2016: Nature Communications
https://www.readbyqxmd.com/read/27303919/overexpression-of-parkin-rescues-the-defective-mitochondrial-phenotype-and-the-increased-apoptosis-of-cockayne-syndrome-a-cells
#20
Barbara Pascucci, Mariarosaria D'Errico, Alessandra Romagnoli, Chiara De Nuccio, Miriam Savino, Donatella Pietraforte, Manuela Lanzafame, Angelo Salvatore Calcagnile, Paola Fortini, Sara Baccarini, Donata Orioli, Paolo Degan, Sergio Visentin, Miria Stefanini, Ciro Isidoro, Gian Maria Fimia, Eugenia Dogliotti
The ERCC8/CSA gene encodes a WD-40 repeat protein (CSA) that is part of a E3-ubiquitin ligase/COP9 signalosome complex. When mutated, CSA causes the Cockayne Syndrome group A (CS-A), a rare recessive progeroid disorder characterized by sun sensitivity and neurodevelopmental abnormalities. CS-A cells features include ROS hyperproduction, accumulation of oxidative genome damage, mitochondrial dysfunction and increased apoptosis that may contribute to the neurodegenerative process. In this study, we show that CSA localizes to mitochondria and specifically interacts with the mitochondrial fission protein dynamin-related protein (DRP1) that is hyperactivated when CSA is defective...
June 9, 2016: Oncotarget
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