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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
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
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
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
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
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
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
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
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
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
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
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
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...
2016: Nature Communications
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
Weiyu Zhang, Peiling Ni, Chunlin Mou, Yanqin Zhang, Hongchao Guo, Tong Zhao, Yuin-Han Loh, Lingyi Chen
The COP9 signalosome has been implicated in pluripotency maintenance of human embryonic stem cells. Yet, the mechanism for the COP9 signalosome to regulate pluripotency remains elusive. Through knocking down individual COP9 subunits, we demonstrate that Cops2, but not the whole COP9 signalosome, is essential for pluripotency maintenance in mouse embryonic stem cells. Down-regulation of Cops2 leads to reduced expression of pluripotency genes, slower proliferation rate, G2/M cell cycle arrest, and compromised embryoid differentiation of embryonic stem cells...
2016: Scientific Reports
Mijin Kim, Tae-Hee Kim, Hae-Hyeog Lee
The Jun activation-domain binding protein 1 (Jab1) recognize a potential coactivator of activator protein 1 (AP-1) such as c-fos, c-jun transcription factor and the fifth subunit of the COP9 signalosome complex. Also, Jab1 activate the c-jun gene resulted cell proliferation. Not only a powerful tumor suppressor but also regulator of apoptosis negative cdk inhibitor p27(kip1) are involved in the cell cycle. This is Jab1 and p27(kip1) interact with each other, Jab1 accelerate p27(kip1) from nuclear to cytoplasm through ubiquitin/proteasome pathway...
April 2016: Journal of Menopausal Medicine
Song Tan, Fang Liu, Xiao-Xi Pan, Yue-Peng Zang, Fei Jin, Wei-Xi Zu, Xiao-Ting Qi, Wei Xiao, Li-Ping Yin
The COP9 signalosome (CSN) plays an important role in proteasome-mediated degradation by regulating CUL1 rubylation of the SCF ligase and is involved in many crucial biological processes. Here, we demonstrate a link between IDEF1 accumulation and the decline in COP9 derubylation activity in response to iron deficiency (-Fe) in rice (Oryza sativa). CSN6 expression is rapidly down-regulated during Fe depletion, contributing to reduced CSN activity, as judged by CSN5 and CUL1 expression, indicating CSN6 is involved in the early stage response of -Fe...
2016: Scientific Reports
Emilio J Sanchez-Barcelo, Maria D Mediavilla, Jerry Vriend, Russel J Reiter
The ubiquitin proteasome system has been proposed as a possible mechanism involved in the multiple actions of melatonin. COP1 (constitutive photomorphogenesis protein 1), a RING finger-type ubiquitin E3 ligase formerly identified in Arabidopsis, is a central switch for the transition from plant growth underground in darkness (etiolation) to growth under light exposure (photomorphogenesis). In darkness, COP1 binds to photomorphogenic transcription factors driving its degradation via the 26S proteasome; blue light, detected by cryptochromes, and red and far-red light detected by phytochromes, negatively regulate COP1...
August 2016: Journal of Pineal Research
João Simões, Ana R Bezerra, Gabriela R Moura, Hugo Araújo, Ivo Gut, Mónica Bayes, Manuel A S Santos
The ascomycete Candida albicans is a normal resident of the gastrointestinal tract of humans and other warm-blooded animals. It occurs in a broad range of body sites and has high capacity to survive and proliferate in adverse environments with drastic changes in oxygen, carbon dioxide, pH, osmolarity, nutrients, and temperature. Its biology is unique due to flexible reassignment of the leucine CUG codon to serine and synthesis of statistical proteins. Under standard growth conditions, CUG sites incorporate leucine (3% of the times) and serine (97% of the times) on a proteome wide scale, but leucine incorporation fluctuates in response to environmental stressors and can be artificially increased up to 98%...
2016: Frontiers in Microbiology
Emanuel Barth, Ron Hübler, Aria Baniahmad, Manja Marz
The COP9 signalosome (CSN) is a highly conserved protein complex, recently being crystallized for human. In mammals and plants the COP9 complex consists of nine subunits, CSN 1-8 and CSNAP. The CSN regulates the activity of culling ring E3 ubiquitin and plays central roles in pleiotropy, cell cycle, and defense of pathogens. Despite the interesting and essential functions, a thorough analysis of the CSN subunits in evolutionary comparative perspective is missing. Here we compared 61 eukaryotic genomes including plants, animals, and yeasts genomes and show that the most conserved subunits of eukaryotes among the nine subunits are CSN2 and CSN5...
2016: Genome Biology and Evolution
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