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Yang Hong, Xiaobo Huang, Lizhe An, Haiyun Ye, Kai Ma, Fengshi Zhang, Qingquan Xu
The third subunit of the COP9 signalosome (COPS3) is associated with cell proliferation and tumorigenesis process in cancer. The present study showed that the expression level of COPS3 was upregulated in malignant cell lines and COPS3 overexpression was related with clinical stage, T stage, historical grade. Kaplan-Meier survival curves showed that COPS3 may function as a prognostic factor for overall survival. CCK-8 and colony formation assays revealed that knockdown of COPS3 in ACHN and 786-O significantly impacted proliferation in vitro...
February 22, 2018: Experimental Cell Research
Dan Jin, Ming Wu, Bosheng Li, Birte Bücker, Philipp Keil, Shaoman Zhang, Jigang Li, Dingming Kang, Jie Liu, Jie Dong, Xing Wang Deng, Vivian Irish, Ning Wei
The control of seed germination and seed dormancy are critical for the successful propagation of plant species, and are important agricultural traits. Seed germination is tightly controlled by the balance of gibberellin (GA) and abscisic acid (ABA), and is influenced by environmental factors. The COP9 Signalosome (CSN) is a conserved multi-subunit protein complex that is best known as a regulator of the Cullin-RING family of ubiquitin E3 ligases (CRLs). Multiple viable mutants of the CSN showed poor germination, except for csn5b-1...
February 20, 2018: PLoS Genetics
Wei Xu, Hao Liu, Zhi-Gang Liu, Hong-Sheng Wang, Fan Zhang, Hao Wang, Ji Zhang, Jing-Jing Chen, Hong-Jun Huang, Yuan Tan, Meng-Ting Cao, Jun Du, Qiu-Gui Zhang, Guan-Min Jiang
Hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related mortality. Resection and transplantation are the only curative treatments available, but are greatly hampered by high recurrence rates. Histone deacetylase inhibitors (HDACIs) are considered to be promising anticancer agents in drug development. Currently, four HDACIs have been granted Food and Drug Administration (FDA) approval for cancer. HDACIs have shown significant efficacy in hematological malignancies. However, they have limited effects in epithelial cell-derived cancers, including HCC, and the mechanisms of these are not elucidated...
January 30, 2018: Cancer Letters
Yuanyuan Xie, Zhen Cao, Elissa Wp Wong, Youxin Guan, Wenfu Ma, Jenny Q Zhang, Edward G Walczak, Devan Murphy, Leili Ran, Inna Sirota, Shangqian Wang, Shipra Shukla, Dong Gao, Simon Rv Knott, Kenneth Chang, Justin Leu, John Wongvipat, Cristina R Antonescu, Gregory Hannon, Ping Chi, Yu Chen
Aberrant activation of MAPK signaling leads to activation of oncogenic transcriptomes. How MAPK signaling is coupled with transcriptional response in cancer is not fully understood. In gastrointestinal stromal tumor and melanoma, both with oncogenic MAPK activation, we find that ETV1 and other Pea3-ETS transcription factors are critical nuclear effectors of MAPK signaling that are regulated through protein stability. Expression of stabilized Pea3-ETS factors can partially rescue the MAPK transcriptome and cell viability after MAPK inhibition...
January 23, 2018: Journal of Clinical Investigation
Annabelle Suisse, Miklós Békés, Tony T Huang, Jessica E Treisman
The COP9 signalosome inhibits the activity of Cullin-RING E3 ubiquitin ligases by removing Nedd8 modifications from their Cullin subunits. Neddylation renders these complexes catalytically active, but deneddylation is also necessary for them to exchange adaptor subunits and avoid auto-ubiquitination. Although deneddylation is thought to be the primary function of the COP9 signalosome, additional activities have been ascribed to some of its subunits. We recently showed that COP9 subunits protect the transcriptional repressor and tumor suppressor Capicua from two distinct modes of degradation...
January 22, 2018: Fly
Justyna Korczeniewska, Betsy J Barnes
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability...
February 1, 2018: Molecular and Cellular Biology
Rui Wang, Yuxing Cai, Baoping Zhang, Zhengxia Wu
The present study aimed to perform screening of a gene signature for the discrimination and prognostic prediction of stage I and II lung squamous carcinoma. A microarray meta‑analysis was performed to identify differentially expressed genes (DEGs) between stage I and II lung squamous carcinoma samples in seven microarray datasets collected from the Gene Expression Omnibus database via the MetaQC and MetaDE package in R. The important DEGs were selected according to the betweenness centrality value of the protein‑protein interaction (PPI) network...
December 19, 2017: International Journal of Molecular Medicine
Ying Li, Zhuannan Chu, Jinying Luo, Yuhong Zhou, Yujing Cai, Yongen Lu, Junhui Xia, Hanhui Kuang, Zhibiao Ye, Bo Ouyang
Abiotic stresses are a major cause of crop loss. Ascorbic acid (AsA) promotes stress tolerance by scavenging reactive oxygen species (ROS), which accumulate when plants experience abiotic stress. Although the biosynthesis and metabolism of AsA are well established, the genes that regulate these pathways remain largely unexplored. Here, we report on a novel regulatory gene from tomato (Solanum lycopersicum) named SlZF3 that encodes a Cys2/His2-type zinc-finger protein with an EAR repression domain. The expression of SlZF3 was rapidly induced by NaCl treatments...
November 28, 2017: Plant Biotechnology Journal
Justyna Korczeniewska, Betsy J Barnes
No abstract text is available yet for this article.
December 15, 2017: Molecular and Cellular Biology
Biruhalem Taye, Dawn Yeo, Raphael Tze Chuen Lee, Boon Huan Tan, Richard J Sugrue, Sebastian Maurer-Stroh
Low pathogenic avian influenza (LPAI) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. Here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (H1N1/WSN, H5N2/F59, H5N2/F118, H5N2/F189, H5N3 and H9N2). Comprehensive microarray probe set re-annotation and ortholog mapping of the host genes was necessary to allow comparison over extended functionally annotated gene sets and orthologous pathways...
November 1, 2017: International Journal of Molecular Sciences
Qingqing Liu, Yike Zhou, Ruiqi Tang, Xuehong Wang, Qiwen Hu, Ying Wang, Qun He
The dynamic SCF (Skp1-cullin1-F-box protein) assembly is controlled by cycles of cullin neddylation/deneddylation based on the deneddylation activity of the COP9 signalosome (CSN) and global sequestration of cullins by CAND1. However, acceptance of this prediction was hampered by the results of recent studies, and the regulatory mechanism and key players remain to be identified. We found that maintaining a proper Cul1Nedd8 /Cul1 ratio is crucial to ensure SCF functions. Reducing the high Cul1Nedd8 /Cul1 ratios in csn mutants through ectopic expression of the nonneddylatable Cul1K722R proteins or introducing the endogenous cul1 K722R point mutation significantly rescues their defective phenotypes...
December 1, 2017: Molecular and Cellular Biology
Hongqin Zhang, Ailing Zhong, Jiajun Sun, Miaomiao Chen, Suhong Xie, Hui Zheng, Yanchun Wang, Yiwen Yu, Lin Guo, Renquan Lu
The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27...
November 4, 2017: Biochemical and Biophysical Research Communications
Nicole Ann Najor, Gillian Nicole Fitz, Jennifer Leigh Koetsier, Lisa Marie Godsel, Lauren Veronica Albrecht, Robert Harmon, Kathleen Janee Green
Cell junctions are scaffolds that integrate mechanical and chemical signaling. We previously showed that a desmosomal cadherin promotes keratinocyte differentiation in an adhesion-independent manner by dampening Epidermal Growth Factor Receptor (EGFR) activity. Here we identify a potential mechanism by which desmosomes assist the de-neddylating COP9 signalosome (CSN) in attenuating EGFR through an association between the Cops3 subunit of the CSN and desmosomal components, Desmoglein1 (Dsg1) and Desmoplakin (Dp), to promote epidermal differentiation...
September 11, 2017: ELife
Ludmila Gaspar, Cedric Howald, Konstantin Popadin, Bert Maier, Daniel Mauvoisin, Ermanno Moriggi, Maria Gutierrez-Arcelus, Emilie Falconnet, Christelle Borel, Dieter Kunz, Achim Kramer, Frederic Gachon, Emmanouil T Dermitzakis, Stylianos E Antonarakis, Steven A Brown
The importance of natural gene expression variation for human behavior is undisputed, but its impact on circadian physiology remains mostly unexplored. Using umbilical cord fibroblasts, we have determined by genome-wide association how common genetic variation impacts upon cellular circadian function. Gene set enrichment points to differences in protein catabolism as one major source of clock variation in humans. The two most significant alleles regulated expression of COPS7B, a subunit of the COP9 signalosome...
September 4, 2017: ELife
Ammara Abdullah, Kathleen M Eyster, Travis Bjordahl, Peng Xiao, Erliang Zeng, Xuejun Wang
Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases Background: The COP9 signalosome (CSN) consisting of 8 unique protein subunits (COPS1 through COPS8) serves as the cullin deneddylase, regulating the catalytic dynamics of cullin RING ligases (CRLs), the largest family of ubiquitin ligases. Supported primarily by the decrease of substrate receptor (SR) proteins of CRLs in cells deficient of a CSN subunit, CSN-mediated cullin deneddylation is believed to prevent autoubiquitination and self-destruction of the SR in active CRLs...
2017: Frontiers in Physiology
Yanjing Zheng, Ke Ma, Haining Lyu, Ying Huang, Hongwei Liu, Ling Liu, Yongsheng Che, Xingzhong Liu, Huixi Zou, Wen-Bing Yin
By deleting the COP9 signalosome subunit PfcsnE from Pestalotiopsis fici, seven compounds that were newly produced by the mutant could be characterized, including five new structures, pestaloficins A-E (1 and 3-6). Pestaloficin A (1) represents a new type of dimeric cyclohexanone derivative linked through an unprecedented pentacyclic spiral ring.
August 24, 2017: Organic Letters
Seckin Eroglu, Emre Aksoy
In plant cells, either excess or insufficient iron (Fe) concentration triggers stress responses, therefore it is strictly controlled. Proteasome-mediated degradation through ubiquitination of Fe homeostasis proteins has just become the focus of research in recent years. Deactivating ubiquitin ligases, COP9 signalosome has a central importance in the translational control of various stress responses. The aim of the study was to investigate COP9 signalosome in Fe deficiency response of Strategy I plants. In silico analysis of a set of Fe-deficiency-responsive genes was conducted against the transcriptome of Arabidopsis csn mutant lines using Genevestigator software...
October 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Daniel Ioan Pacurar, Monica Lacramioara Pacurar, Abdellah Lakehal, Andrea Mariana Pacurar, Alok Ranjan, Catherine Bellini
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
July 20, 2017: Scientific Reports
Mariam A Ba, Jeffrey Surina, Cherie A Singer, Maria L Valencik
BACKGROUND: The COP9 signalosome (CSN) is a conserved protein complex composed of 8 subunits designated CSN1-CSN8. CSN3 represents the third subunit of the CSN and maintains the integrity of the complex. CSN3 binds to the striated muscle-specific β1D integrin tail, and its subcellular localization is altered in differentiated skeletal muscle cells. However, the role of CSN3 in skeletal muscle differentiation is unknown. The main goal of this study was to identify whether CSN3 participates in myoblast differentiation and the signalling mechanisms involved using C2C12 cells as a skeletal muscle cell model...
June 17, 2017: BMC Pharmacology & Toxicology
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the Drosophila COP9 signalosome subunit 1b ( CSN1b ) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
July 15, 2017: Development
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