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https://www.readbyqxmd.com/read/29676528/e3-ubiquitin-ligase-rnf123-targets-lamin-b1-and-lamin-binding-proteins
#1
Richa Khanna, Vidhya Krishnamoorthy, Veena K Parnaik
Lamins are key nuclear proteins which are important for maintaining nuclear structure and function. Mutations in lamins cause a spectrum of genetic diseases termed as laminopathies. RING finger containing E3 ubiquitin ligase, RNF123 is transcriptionally upregulated in cells expressing rod-domain lamin A mutations. However, the functional relevance of RNF123 in laminopathic cells is not clear. Using a mass spectrometry based approach, we identified lamins and lamin-binding proteins retinoblastoma protein (pRb), lamina-associated polypeptide 2α (LAP2α) and emerin as RNF123-interacting proteins...
April 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29674674/the-e3-ubiquitin-ligase-pellino2-mediates-priming-of-the-nlrp3-inflammasome
#2
Fiachra Humphries, Ronan Bergin, Ruaidhri Jackson, Nezira Delagic, Bingwei Wang, Shuo Yang, Alice V Dubois, Rebecca J Ingram, Paul N Moynagh
The NLRP3 inflammasome has an important function in inflammation by promoting the processing of pro-IL-1β and pro-IL-18 to their mature bioactive forms, and by inducing cell death via pyroptosis. Here we show a critical function of the E3 ubiquitin ligase Pellino2 in facilitating activation of the NLRP3 inflammasome. Pellino2-deficient mice and myeloid cells have impaired activation of NLRP3 in response to toll-like receptor priming, NLRP3 stimuli and bacterial challenge. These functions of Pellino2 in the NLRP3 pathway are dependent on Pellino2 FHA and RING-like domains, with Pellino2 promoting the ubiquitination of NLRP3 during the priming phase of activation...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29673441/ywhaz-binds-to-trim21-but-is-not-involved-in-trim21-stimulated-osteosarcoma-cell-proliferation
#3
Qing Zhong Zeng, Wan Ting Liu, Jun Lei Lu, Xiao Hui Liu, Yun Fang Zhang, Lang Xia Liu, Xue Juan Gao
OBJECTIVE: Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation. METHODS: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened...
March 2018: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29673126/overexpression-of-hace1-in-gastric-cancer-inhibits-tumor-aggressiveness-by-impeding-cell-proliferation-and-migration
#4
Ying-Ling Chen, Dong-Ping Li, Hong-Yue Jiang, Yang Yang, Li-Li Xu, Shun-Cai Zhang, Hong Gao
HACE1 E3 ligase was discovered to be down-regulated in several cancers while its role in regulating tumors was merely understood. This study aimed to explore the specific effect of HACE1 played in gastric tumorigenesis and its potential mechanism. HACE1's expression was found significantly lower in gastric cancer tissues compared with the adjacent normal tissues (P < 0.001). Its protein level in gastric cancer negatively correlated to tumor pathological differentiation (P = 0.019). And in gastric cancer patients with TNM I-IIIa, those with lower HACE1 protein level had poorer overall survival (P = 0...
April 19, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29671242/fbxw7%C3%AE-is-an-inducing-mediator-of-dexamethasone-induced-skeletal-muscle-atrophy-in-vivo-with-the-axis-of-fbxw7%C3%AE-myogenin-atrogenes
#5
Kyungshin Shin, Young-Gyu Ko, Jaemin Jeong, Heechung Kwon
Muscle atrophy is induced by several pathways, e.g., it can be attributed to inherited cachectic symptoms, genetic disorders, sarcopenia, or chronic side effects of treatments. However, the underlying regulatory mechanisms that contribute to muscle atrophy have not been fully elucidated. In this study, we evaluated the role of Fbxw7β, an ubiquitin E3 ligase, in a dexamethasone-induced muscle atrophy model. In this model, endogenous Fbxw7β was up-regulated; furthermore, the Fbxw7β-myogenin-atrogene axis was upregulated, supporting our previous results linking Fbxw7β to muscle atrophy in vitro...
April 18, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29667579/intracellular-antibody-signalling-is-regulated-by-phosphorylation-of-the-fc-receptor-trim21
#6
Claire Dickson, Adam J Fletcher, Marina Vaysburd, Ji-Chun Yang, Donna L Mallery, Jingwei Zeng, Christopher M Johnson, Stephen H McLaughlin, Mark Skehel, Sarah Maslen, James Cruickshank, Nicolas Huguenin-Dezot, Jason W Chin, David Neuhaus, Leo C James
Cell surface Fc receptors activate inflammation and are tightly controlled to prevent autoimmunity. Antibodies also simulate potent immune signalling from inside the cell via the cytosolic antibody receptor TRIM21, but how this is regulated is unknown. Here we show that TRIM21 signalling is constitutively repressed by its B-Box domain and activated by phosphorylation. The B-Box occupies an E2 binding site on the catalytic RING domain by mimicking E2-E3 interactions, inhibiting TRIM21 ubiquitination and preventing immune activation...
April 18, 2018: ELife
https://www.readbyqxmd.com/read/29667067/a-first-in-class-inhibitor-mln4924-pevonedistat-induces-cell-cycle-arrest-senescence-and-apoptosis-in-human-renal-cell-carcinoma-by-suppressing-ube2m-dependent-neddylation-modification
#7
Bo Xu, Yuyou Deng, Ran Bi, Haoran Guo, Chang Shu, Neelam Kumari Shah, Junliang Chang, Guanchen Liu, Yujun Du, Wei Wei, Chunxi Wang
PURPOSE: MLN4924 is a second-generation inhibitor that targets ubiquitin-proteasome system by inhibiting neddylation activation enzyme (NAE), and subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs), which leads to the accumulation of CRLs substrates and hence, suppressing diverse tumor development. In this study, we investigated the potential application of this first-in-class inhibitor MLN4924 in the treatment of human renal cell carcinoma both in vitro and in vivo...
April 17, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29666278/deubiquitylation-and-stabilization-of-p21-by-usp11-is-critical-for-cell-cycle-progression-and-dna-damage-responses
#8
Tanggang Deng, Guobei Yan, Xin Song, Lin Xie, Yu Zhou, Jianglin Li, Xiaoxiao Hu, Zhen Li, Jun Hu, Yibin Zhang, Hui Zhang, Yang Sun, Peifu Feng, Dong Wei, Bin Hu, Jing Liu, Weihong Tan, Mao Ye
p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell-cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligase complexes is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29665313/refinement-of-the-endogenous-epitope-tagging-eet-technology-allows-the-identification-of-a-novel-nras-binding-partner-in-melanoma
#9
Michal Alon, Rafi Emmanuel, Nouar Qutob, Anna Bakhman, Victoria Peshti, Alexandra Brodezki, David Bassan, Mickey Kosloff, Yardena Samuels
The NRAS oncoprotein is highly mutated in melanoma. However, to date, no comprehensive proteomic study has been reported for NRAS. Here we utilized the Endogenous Epitope Tagging (EET) approach for the identification of novel NRAS binding partners. Using EET, an epitope tag is added to the endogenously expressed protein, via modification of its genomic coding sequence. Existing EET systems are not robust, suffer from high background and are labor-intensive. To this end, we present a polyadenylation signal-trap construct for N'-tagging, that generates a polycistronic mRNA with the gene of interest...
April 17, 2018: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29665074/parkin-deficiency-modulates-nlrp3-inflammasome-activation-by-attenuating-an-a20-dependent-negative-feedback-loop
#10
François Mouton-Liger, Thibault Rosazza, Julia Sepulveda-Diaz, Amélie Ieang, Sidi-Mohamed Hassoun, Emilie Claire, Graziella Mangone, Alexis Brice, Patrick P Michel, Jean-Christophe Corvol, Olga Corti
Neuroinflammation and mitochondrial dysfunction, key mechanisms in the pathogenesis of Parkinson's disease (PD), are usually explored independently. Loss-of-function mutations of PARK2 and PARK6, encoding the E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1, account for a large proportion of cases of autosomal recessive early-onset PD. PINK1 and Parkin regulate mitochondrial quality control and have been linked to the modulation of innate immunity pathways. We report here an exacerbation of NLRP3 inflammasome activation by specific inducers in microglia and bone marrow-derived macrophages from Park2-/- and Pink1-/- mice...
April 17, 2018: Glia
https://www.readbyqxmd.com/read/29662198/the-mir-106b-25-cluster-mediates-breast-tumor-initiation-through-activation-of-notch1-via-direct-repression-of-nedd4l
#11
A L Guarnieri, C G Towers, D J Drasin, M U J Oliphant, Z Andrysik, T J Hotz, R L Vartuli, E S Linklater, A Pandey, S Khanal, J M Espinosa, H L Ford
Tumor-initiating cells (TIC) represent a subset of tumor cells with increased self-renewal capability. TICs display resistance to frontline cancer treatment and retain the ability to repopulate a tumor after therapy, leading to cancer relapse. NOTCH signaling has been identified as an important driver of the TIC population, yet mechanisms governing regulation of this pathway in cancer remain to be fully elucidated. Here we identify a novel mechanism of NOTCH regulation and TIC induction in breast cancer via the miR-106b-25 miRNA cluster...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29662028/nitrate-reductases-are-relocalized-to-the-nucleus-by-atsiz1-and-their-levels-are-negatively-regulated-by-cop1-and-ammonium
#12
Joo Yong Kim, Bong Soo Park, Sang Woo Park, Han Yong Lee, Jong Tae Song, Hak Soo Seo
Nitrate reductases (NRs) catalyze the first step in the reduction of nitrate to ammonium. NR activity is regulated by sumoylation through the E3 ligase activity of AtSIZ1. However, it is not clear how NRs interact with AtSIZ1 in the cell, or how nitrogen sources affect NR levels and their cellular localization. Here, we show that the subcellular localization of NRs is modulated by the E3 SUMO (Small ubiquitin-related modifier) ligase AtSIZ1 and that NR protein levels are regulated by nitrogen sources. Transient expression analysis of GFP fusion proteins in onion epidermal cells showed that the NRs NIA1 and NIA2 localize to the cytoplasmic membrane, and that AtSIZ1 localizes to the nucleoplasm, including nuclear bodies, when expressed separately, whereas NRs and AtSIZ1 localize to the nucleus when co-expressed...
April 15, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29661351/novel-insights-into-e3-ubiquitin-ligase-in-cancer-chemoresistance
#13
REVIEW
Li Yang, Jing Chen, Xi Huang, Enfan Zhang, Jingsong He, Zhen Cai
Drug resistance can obstruct successful cancer chemotherapy. The ubiquitin-proteasome pathway has emerged as a crucial player that controls steady-state protein levels regulating multiple biological processes, such as cell cycle, cellular proliferation, apoptosis, and DNA damage response, which are involved in oncogenesis, cancer development, prognosis, and drug resistance. E3 ligases perform the final step in the ubiquitination cascade, and determine which protein becomes ubiquitylated by specifically binding the substrate protein...
April 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#14
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29658272/arsenite-targets-the-ring-finger-domain-of-rbx1-e3-ubiquitin-ligase-to-inhibit-proteasome-mediated-degradation-of-nrf2
#15
Ji Jiang, Lok Ming Tam, Pengcheng Wang, Yinsheng Wang
Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response signaling pathway is a major mechanism for the cellular defense against oxidative stress. Arsenite, a widespread contaminant in drinking water, is known to induce oxidative stress and activate Nrf2-dependent signaling pathway through stabilization of Nrf2 protein by inhibiting its ubiquitination via the Cul3-Rbx1-Keap1 (cullin 3, RING-box 1, and Kelch-like ECH-associated protein 1) E3 ubiquitin ligase and its degradation by the 26S proteasome, though the underlying mechanism remains elusive...
April 16, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29656896/opposite-roles-of-salicylic-acid-receptors-npr1-and-npr3-npr4-in-transcriptional-regulation-of-plant-immunity
#16
Yuli Ding, Tongjun Sun, Kevin Ao, Yujun Peng, Yaxi Zhang, Xin Li, Yuelin Zhang
Salicylic acid (SA) is a plant defense hormone required for immunity. Arabidopsis NPR1 and NPR3/NPR4 were previously shown to bind SA and all three proteins were proposed as SA receptors. NPR1 functions as a transcriptional co-activator, whereas NPR3/NPR4 were suggested to function as E3 ligases that promote NPR1 degradation. Here we report that NPR3/NPR4 function as transcriptional co-repressors and SA inhibits their activities to promote the expression of downstream immune regulators. npr4-4D, a gain-of-function npr4 allele that renders NPR4 unable to bind SA, constitutively represses SA-induced immune responses...
April 11, 2018: Cell
https://www.readbyqxmd.com/read/29655804/characterization-of-wdr20-a-new-regulator-of-the-erad-machinery
#17
Lin-Gao Ju, Xiang Lin, Dong Yan, Qing-Lan Li, Min Wu, Lian-Yun Li
ERAD is an important process of protein quality control that eliminates misfolded or unassembled proteins from ER. Before undergoing proteasome degradation, the misfolded proteins are dislocated from ER membrane into cytosol, which requires the AAA ATPase p97/VCP and its cofactor, the NPL4-UFD1 dimer. Here, we performed a CRISPR-based screen and identify many candidates for ERAD regulation. We further confirmed four proteins, FBOX2, TRIM6, UFL1 and WDR20, are novel regulators for ERAD. Then the molecular mechanism for WDR20 in ERAD is further characterized...
April 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29653302/jembrana-disease-virus-vif-antagonizes-the-inhibition-of-bovine-apobec3-proteins-through-ubiquitin-mediate-protein-degradation
#18
Xing Su, Hong Wang, Xiaohong Zhou, Zhaolong Li, Baisong Zheng, Wenyan Zhang
Viral infectivity factor (Vif) encoded by lentiviruses is essential for viral replication and escaping from antiviral activity of host defensive factors APOBEC3. Jembrana disease virus (JDV) causes an acute disease syndrome with approximately 20% case fatality rate in Bali cattle. However, the interplay mechanism between JDV Vif and Bos taurus APOBEC3 (btA3) is poorly understood. In this study, we determined that JDV Vif recruits ElonginB, ElonginC(ELOB/C), Cul2 and RBX1 but without the need of CBF-β to form E3 ubiquitin ligase and induces the degradation of btA3 proteins...
April 10, 2018: Virology
https://www.readbyqxmd.com/read/29651950/roles-of-traf6-in-central-nervous-system
#19
Yang Dou, Xiaodi Tian, Jian Zhang, Zhong Wang, Gang Chen
Tumor necrosis factor receptor-associated factor (TRAF) is an important binding protein of tumor necrosis factor (TNF) superfamily and the toll/IL-1 receptor (TIR) superfamily, which play an important role in innate immunity and acquired immunity. TRAFs family has 7 members (TRAF1-7), and TRAF6 has its special facture and biological function. TRAF6 has two special domains: C-terminal domain and N-terminal domain, which could integrate with multiple kinases and regulate signaling pathway function as E3 ubiquitin ligase...
April 11, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29650964/tspan15-interacts-with-btrc-to-promote-oesophageal-squamous-cell-carcinoma-metastasis-via-activating-nf-%C3%AE%C2%BAb-signaling
#20
Baozhu Zhang, Zhao Zhang, Lei Li, Yan-Ru Qin, Haibo Liu, Chen Jiang, Ting-Ting Zeng, Meng-Qing Li, Dan Xie, Yan Li, Xin-Yuan Guan, Ying-Hui Zhu
Beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) is crucial for the degradation of IκBα. Our previous transcriptome sequencing analysis revealed that tetraspanin 15 (TSPAN15) was significantly upregulated in clinical oesophageal squamous cell carcinoma (OSCC) tissues. Here, we show that high TSPAN15 expression in OSCC tissues is significantly associated with lymph node and distant metastasis, advanced clinical stage, and poor prognosis. Elevated TSPAN15 expression is, in part, caused by the reduction of miR-339-5p...
April 12, 2018: Nature Communications
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