keyword
https://read.qxmd.com/read/38466642/cop9-signalosome-complex-is-a-prognostic-biomarker-and-corresponds-with-immune-infiltration-in-hepatocellular-carcinoma
#1
JOURNAL ARTICLE
Jiahui Liu, Dexing Han, Junfeng Xuan, Jinye Xie, Weijia Wang, Quan Zhou, Kang Chen
Hepatocellular carcinoma (HCC) is among the most common deadly tumors but still lacks specific biomarkers for diagnosis, prognosis, and treatment guidance. The COP9 signalosome (COPS) is an essential regulator of the ubiquitin conjugation pathway upregulated in various cancers. We evaluated the contributions of COPS subunits to HCC tumorigenesis and their utility for prognosis. We comprehensively evaluated the tumor expression pattern and tumorigenic functions of COPS subunits using The Cancer Genome Atlas (TCGA), The Human Protein Atlas and immunohistochemistry...
March 11, 2024: Aging
https://read.qxmd.com/read/38464205/the-ubiquitin-ligase-rbx2-sag-regulates-mitochondrial-ubiquitination-and-mitophagy
#2
Wenjuan Wang, Ermin Li, Jianqiu Zou, Qu Chen, Juan Ayala, Yuan Wen, Md Sadikul Islam, Neal L Weintraub, David J Fulton, Qiangrong Liang, Jiliang Zhou, Jinbao Liu, Jie Li, Yi Sun, Huabo Su
UNLABELLED: Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. While the role of ubiquitin (Ub) ligase PARKIN in mitophagy has been extensively studied, increasing evidence suggests the existence of PARKIN-independent mitophagy in highly metabolically active organs such as the heart. Here, we identify a crucial role for Cullin-RING Ub ligase 5 (CRL5) in basal mitochondrial turnover in cardiomyocytes. CRL5 is a multi-subunit Ub ligase comprised by the catalytic RING box protein RBX2 (also known as SAG), scaffold protein Cullin 5 (CUL5), and a substrate-recognizing receptor...
February 28, 2024: bioRxiv
https://read.qxmd.com/read/38427913/cop9-signalosome-component-csn-5-stabilizes-puf-proteins-fbf-1-and-fbf-2-in-caenorhabditis-elegans-germline-stem-and-progenitor-cells
#3
JOURNAL ARTICLE
Emily Osterli, Mary Ellenbecker, Xiaobo Wang, Mikaya Terzo, Ketch Jacobson, DeAnna Cuello, Ekaterina Voronina
RNA-binding proteins FBF-1 and FBF-2 (FBFs) are required for germline stem cell maintenance and the sperm/oocyte switch in Caenorhabditis elegans, though the mechanisms controlling FBF protein levels remain unknown. We identified an interaction between both FBFs and CSN-5, a component of the COP9 (constitutive photomorphogenesis 9) signalosome best known for its role in regulating protein degradation. Here, we find that the Mpr1/Pad1 N-terminal metalloprotease domain of CSN-5 interacts with the Pumilio and FBF RNA-binding domain of FBFs and the interaction is conserved for human homologs CSN5 and PUM1...
March 1, 2024: Genetics
https://read.qxmd.com/read/38385070/a-novel-csn5-crt-o-glcnac-er-stress-regulatory-axis-in-platinum-resistance-of-epithelial-ovarian-cancer
#4
JOURNAL ARTICLE
Tianqing Yan, Xiaolu Ma, Kaixia Zhou, Jiazhen Cao, Yanan Tian, Hui Zheng, Ying Tong, Suhong Xie, Yanchun Wang, Lin Guo, Renquan Lu
Background: High levels of COP9 signalosome subunit 5 (CSN5) in epithelial ovarian cancer (EOC) are associated with poor prognosis and are implicated in mediating platinum resistance in EOC cells. The underlying mechanisms, however, remained undefined. This study aimed to elucidate the molecular process and identify potential therapeutic targets. Methods: RNA-sequencing was used to investigate differentially expressed genes between platinum-resistant EOC cells with CSN5 knockdown and controls. O-GlcNAc proteomics were employed to identify critical modulators downstream of CSN5...
2024: International Journal of Biological Sciences
https://read.qxmd.com/read/38381201/oscsn2-orchestrates-oryza-sativa-l-growth-and-development-through-modulation-of-the-ga-and-br-pathways
#5
JOURNAL ARTICLE
Shining Han, Weijie Yue, Anar Bao, Tongtong Jiao, Yanxi Liu, Hua Zeng, Kai Song, Ming Wu, Liquan Guo
The COP9 signalosome (CSN) is a conserved protein complex found in higher eukaryotes, consisting of eight subunits, and it plays a crucial role in regulating various processes of plant growth and development. Among these subunits, CSN2 is one of the most conserved components within the COP9 signalosome complex. Despite its prior identification in other species, its specific function in Oryza sativa L. (Rice) has remained poorly understood. In this study, we investigated the role of CSN2 in rice using gene editing CRISPR/Cas9 technology and overexpression techniques...
February 21, 2024: Functional & Integrative Genomics
https://read.qxmd.com/read/38358979/topic-prediction-for-tobacco-control-based-on-cop9-tweets-using-machine-learning-techniques
#6
JOURNAL ARTICLE
Sherif Elmitwalli, John Mehegan, Georgie Wellock, Allen Gallagher, Anna Gilmore
The prediction of tweets associated with specific topics offers the potential to automatically focus on and understand online discussions surrounding these issues. This paper introduces a comprehensive approach that centers on the topic of "harm reduction" within the broader context of tobacco control. The study leveraged tweets from the period surrounding the ninth Conference of the Parties to review the Framework Convention on Tobacco Control (COP9) as a case study to pilot this approach. By using Latent Dirichlet Allocation (LDA)-based topic modeling, the study successfully categorized tweets related to harm reduction...
2024: PloS One
https://read.qxmd.com/read/38332366/dynamic-molecular-architecture-and-substrate-recruitment-of-cullin3-ring-e3-ligase-crl3-kbtbd2
#7
JOURNAL ARTICLE
Yuxia Hu, Zhao Zhang, Qiyu Mao, Xiang Zhang, Aihua Hao, Yu Xun, Yeda Wang, Lin Han, Wuqiang Zhan, Qianying Liu, Yue Yin, Chao Peng, Eva Marie Y Moresco, Zhenguo Chen, Bruce Beutler, Lei Sun
Phosphatidylinositol 3-kinase α, a heterodimer of catalytic p110α and one of five regulatory subunits, mediates insulin- and insulin like growth factor-signaling and, frequently, oncogenesis. Cellular levels of the regulatory p85α subunit are tightly controlled by regulated proteasomal degradation. In adipose tissue and growth plates, failure of K48-linked p85α ubiquitination causes diabetes, lipodystrophy and dwarfism in mice, as in humans with SHORT syndrome. Here we elucidated the structures of the key ubiquitin ligase complexes regulating p85α availability...
February 8, 2024: Nature Structural & Molecular Biology
https://read.qxmd.com/read/38256025/smc5-6-promotes-replication-fork-stability-via-negative-regulation-of-the-cop9-signalosome
#8
JOURNAL ARTICLE
Michelle J Xu, Philip W Jordan
It is widely accepted that DNA replication fork stalling is a common occurrence during cell proliferation, but there are robust mechanisms to alleviate this and ensure DNA replication is completed prior to chromosome segregation. The SMC5/6 complex has consistently been implicated in the maintenance of replication fork integrity. However, the essential role of the SMC5/6 complex during DNA replication in mammalian cells has not been elucidated. In this study, we investigate the molecular consequences of SMC5/6 loss at the replication fork in mouse embryonic stem cells (mESCs), employing the auxin-inducible degron (AID) system to deplete SMC5 acutely and reversibly in the defined cellular contexts of replication fork stall and restart...
January 12, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38187549/-toxoplasma-gondii-f-box-protein-l2-silences-feline-restricted-genes-necessary-for-sexual-commitment
#9
Carlos G Baptista, Sarah Hosking, Elisabet Gas-Pascual, Loic Ciampossine, Steven Abel, Mohamed-Ali Hakimi, Victoria Jeffers, Karine Le Roch, Christopher M West, Ira J Blader
UNLABELLED: Toxoplasma gondii is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle. However, bradyzoites in intermediate hosts differentiate exclusively to disease-causing tachyzoites, which rapidly disseminate throughout the host...
December 18, 2023: bioRxiv
https://read.qxmd.com/read/38184853/cop9-signalosome-mediated-deneddylation-of-cullin1-is-necessary-for-scf-ebf1-assembly-in-arabidopsis-thaliana
#10
JOURNAL ARTICLE
Jie Dong, Yuanyuan Li, Shuyang Cheng, Xuehui Li, Ning Wei
Functions of the SKP1-CUL1-F box (SCF) ubiquitin E3 ligases are essential in plants. The F box proteins (FBPs) are substrate receptors that recruit substrates and assemble an active SCF complex, but the regulatory mechanism underlying the FBPs binding to CUL1 to activate the SCF cycle is not fully understood. We show that Arabidopsis csn1-10 is defective in SCFEBF1 -mediated PIF3 degradation during de-etiolation, due to impaired association of EBF1 with CUL1 in csn1-10. EBF1 preferentially associates with un-neddylated CUL1 that is deficient in csn1-10 and the EBF1-CUL1 binding is rescued by the neddylation inhibitor MLN4924...
January 6, 2024: Cell Reports
https://read.qxmd.com/read/38059183/computational-exploration-of-the-significance-of-cops6-in-cancer-functional-and-clinical-relevance-across-tumor-types
#11
JOURNAL ARTICLE
Shi-Lin Wang, Guang-Zheng Zhuo, Li-Ping Wang, Xiang-Hu Jiang, Guo-Hong Liu, Yun-Bao Pan, Yi-Rong Li
BACKGROUND: The COP9 signalosome subunit 6 ( COPS6 ) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer...
November 24, 2023: World Journal of Clinical Oncology
https://read.qxmd.com/read/38005759/osjab1-positively-regulates-ascorbate-biosynthesis-and-negatively-regulates-salt-tolerance-due-to-inhibiting-early-stage-salt-induced-ros-accumulation-in-rice
#12
JOURNAL ARTICLE
Jiayi Wang, Chuanyu Zhang, Hua Li, Yuejun Xu, Bo Zhang, Fuyu Zheng, Beiping Zhao, Haiwen Zhang, Hui Zhao, Baohai Liu, Minggang Xiao, Zhijin Zhang
Reactive oxygen species (ROS) play dual roles in plant stress response, but how plants modulate the dual roles of ROS in stress response is still obscure. OsJAB1 ( JUN-activation-domain-binding protein 1 ) encodes the rice CSN5 (COP9 signalsome subunit 5). This study showed that, similar to the Arabidopsis homolog gene CSN5B , OsJAB1 -overexpressing (driven by a CaMV 35S promoter) plants (OEs) impaired rice salt stress tolerance; in contrast, OsJAB1 -inhibited-expression (using RNA-interfering technology) plants (RIs) enhanced rice salt stress tolerance...
November 15, 2023: Plants (Basel, Switzerland)
https://read.qxmd.com/read/37929693/early-flowering-is-a-dominant-gain-of-function-allele-of-fantastic-four-1-2c-that-promotes-early-flowering-in-tomato
#13
JOURNAL ARTICLE
Dedi Zhang, Guo Ai, Kangna Ji, Rong Huang, Chunrui Chen, Zixuan Yang, Jiafa Wang, Long Cui, Guobin Li, Maryam Tahira, Xin Wang, Taotao Wang, Jie Ye, Zonglie Hong, Zhibiao Ye, Junhong Zhang
Flowering time, an important factor in plant adaptability and genetic improvement, is regulated by various genes in tomato (Solanum lycopersicum). In this study, we characterized a tomato mutant, EARLY FLOWERING (EF), that developed flowers much earlier than its parental control. EF is a dominant gain-of-function allele with a T-DNA inserted 139 bp downstream of the stop codon of FANTASTIC FOUR 1/2c (FAF1/2c). The transcript of SlFAF1/2c was at elevated levels in the EF mutant. Overexpressing SlFAF1/2c in tomato plants phenocopied the early flowering trait of the EF mutant...
November 6, 2023: Plant Biotechnology Journal
https://read.qxmd.com/read/37717061/a-plant-cytorhabdovirus-modulates-locomotor-activity-of-insect-vectors-to-enhance-virus-transmission
#14
JOURNAL ARTICLE
Dong-Min Gao, Ji-Hui Qiao, Qiang Gao, Jiawen Zhang, Ying Zang, Liang Xie, Yan Zhang, Ying Wang, Jingyan Fu, Hua Zhang, Chenggui Han, Xian-Bing Wang
Transmission of many plant viruses relies on phloem-feeding insect vectors. However, how plant viruses directly modulate insect behavior is largely unknown. Barley yellow striate mosaic virus (BYSMV) is transmitted by the small brown planthopper (SBPH, Laodelphax striatellus). Here, we show that BYSMV infects the central nervous system (CNS) of SBPHs, induces insect hyperactivity, and prolongs phloem feeding duration. The BYSMV accessory protein P6 interacts with the COP9 signalosome subunit 5 (LsCSN5) of SBPHs and suppresses LsCSN5-regulated de-neddylation from the Cullin 1 (CUL1), hereby inhibiting CUL1-based E3 ligases-mediated degradation of the circadian clock protein Timeless (TIM)...
September 16, 2023: Nature Communications
https://read.qxmd.com/read/37679621/construction-of-an-ultra-large-phage-display-library-by-kunkel-mutagenesis-and-rolling-circle-amplification
#15
JOURNAL ARTICLE
Renhua R Huang, Michael Kierny, Veronica Volgina, Makio Iwashima, Christina Miller, Brian K Kay
An important contributor to the successful generation of recombinant affinity reagents via phage display is a large and diverse library. We describe, herein, the application of Kunkel mutagenesis and rolling circle amplification (RCA) to the construction of a 1.1 × 1011 member library, with only 26 electroporations, and isolation of low- to sub-nanomolar monobodies to a number of protein targets, including human COP9 signalosome subunit 5 (COPS5), HIV-1 Rev. binding protein-like protein (HRBL), X-ray repair cross-complementing 5/6 (Ku70/80) heterodimer, the receptor-binding domain (RBD) of SARS-CoV-2, and transforming growth factor beta 1 (TGF-β1)...
2023: Methods in Molecular Biology
https://read.qxmd.com/read/37603767/fungal-cop9-signalosome-assembly-requires-connection-of-two-trimeric-intermediates-for-integration-of-intrinsic-deneddylase
#16
JOURNAL ARTICLE
Fruzsina Bakti, Helena Stupperich, Kerstin Schmitt, Oliver Valerius, Anna M Köhler, Cindy Meister, Anja Strohdiek, Rebekka Harting, Christoph Sasse, Kai Heimel, Piotr Neumann, Ralf Ficner, Gerhard H Braus
The conserved eight-subunit COP9 signalosome (CSN) is required for multicellular fungal development. The CSN deneddylase cooperates with the Cand1 exchange factor to control replacements of E3 ubiquitin cullin RING ligase receptors, providing specificity to eukaryotic protein degradation. Aspergillus nidulans CSN assembles through a heptameric pre-CSN, which is activated by integration of the catalytic CsnE deneddylase. Combined genetic and biochemical approaches provided the assembly choreography within a eukaryotic cell for native fungal CSN...
August 29, 2023: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/37597109/the-cop9-signalosome-reduces-neuroinflammation-and-attenuates-ischemic-neuronal-stress-in-organotypic-brain-slice-culture-model
#17
JOURNAL ARTICLE
Yuan Tian, Jelena Milic, Laura Sebastián Monasor, Rahul Chakraborty, Sijia Wang, Yue Yuan, Yaw Asare, Christian Behrends, Sabina Tahirovic, Jürgen Bernhagen
The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a deNEDDylase controlling ubiquitination activity of cullin-RING-E3 ligases (CRLs) and thus the levels of key cellular proteins. While the CSN and its catalytic subunit CSN5 have been extensively studied in cancer, its role in inflammatory and neurological diseases is less understood. Following verification that CSN5 is expressed in mouse and human brain, here we studied the role of the CSN in neuroinflammation and ischemic neuronal damage employing models of relevant brain-resident cell types, an ex vivo organotypic brain slice culture model, and the CRL NEDDylation state-modifying drugs MLN4924 and CSN5i-3, which mimic and inhibit, respectively, CSN5 deNEDDylase activity...
August 19, 2023: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/37526651/systematic-analysis-of-the-frazzled-receptor-interactome-establishes-previously-unreported-regulators-of-axon-guidance
#18
JOURNAL ARTICLE
Yixin Zang, Greg J Bashaw
The Netrin receptor Dcc and its Drosophila homolog Frazzled play crucial roles in diverse developmental process, including axon guidance. In Drosophila, Fra regulates midline axon guidance through a Netrin-dependent and a Netrin-independent pathway. However, what molecules regulate these distinct signaling pathways remain unclear. To identify Fra-interacting proteins, we performed affinity purification mass spectrometry to establish a neuronal-specific Fra interactome. In addition to known interactors of Fra and Dcc, including Netrin and Robo1, our screen identified 85 candidate proteins, the majority of which are conserved in humans...
August 1, 2023: Development
https://read.qxmd.com/read/37460146/the-c-terminal-tail-of-csnap-attenuates-the-csn-complex
#19
JOURNAL ARTICLE
Maria G Füzesi-Levi, Gili Ben-Nissan, Dina Listov, Yael Fridmann Sirkis, Zvi Hayouka, Sarel Fleishman, Michal Sharon
Protein degradation is one of the essential mechanisms that enables reshaping of the proteome landscape in response to various stimuli. The largest E3 ubiquitin ligase family that targets proteins to degradation by catalyzing ubiquitination is the cullin-RING ligases (CRLs). Many of the proteins that are regulated by CRLs are central to tumorigenesis and tumor progression, and dysregulation of the CRL family is frequently associated with cancer. The CRL family comprises ∼300 complexes, all of which are regulated by the COP9 signalosome complex (CSN)...
October 2023: Life Science Alliance
https://read.qxmd.com/read/37429009/phytophthora-rxlr-effector-pcsnel4b-promotes-degradation-of-resistance-protein-atrps2
#20
JOURNAL ARTICLE
Huhu Gao, Yuchen Guo, Mengyuan Ren, Lijun Tang, Wenxin Gao, Song Tian, Guangda Shao, Qin Peng, Biao Gu, Jianqiang Miao, Xili Liu
Phytophthora capsici deploys effector proteins to manipulate host immunity and facilitate its colonization. However, the underlying mechanisms remain largely unclear. In this study, we demonstrated that a Sne-like (Snel) RxLR effector gene PcSnel4 is highly expressed at the early stages of P. capsici infection in Nicotiana benthamiana. Knocking out both alleles of PcSnel4 attenuated the virulence of P. capsici, while expression of PcSnel4 promoted its colonization in N. benthamiana. PcSnel4B could suppress the hypersensitive reaction (HR) induced by Avr3a-R3a and RESISTANCE TO PSEUDOMONAS SYRINGAE 2 (AtRPS2), but it did not suppress cell death elicited by Phytophthora infestin 1 (INF1) and Crinkler 4 (CRN4)...
July 11, 2023: Plant Physiology
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