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Alegre Flores-Pérez, Guillermo Elizondo
Human papilloma viruses 16 and 18 express E6 and E7 oncoproteins. E6 activates and redirects E6-associated protein (E6AP), an E3 ubiquitin ligase. E6AP interacts with Ube2l3, an E2 ubiquitin conjugating enzyme protein (also known as UbcH7), to promote p53 ubiquitination and degradation by the 26S proteasome. Therefore, blocking E6-mediated p53 degradation might be an alternative treatment for cervical cancer. In addition, activation of the aryl hydrocarbon receptor (AHR) induces Ube2l3 expression, resulting in p53 ubiquitination and degradation...
February 1, 2018: Chemico-biological Interactions
Xingjie Ma, Junjie Zhao, Fan Yang, Haitao Liu, Weibo Qi
The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth...
October 13, 2017: Oncotarget
J F Liu, J Wang, D D Guo, C J Qi, F R Cao, Z Tian, N J Yao, Y C Wu, Y Yang, Y L He, Y R Zhao, T Y Chen
Objective: To investigate the association between single nucleotide polymorphisms (SNPs) of rs3130542 and rs4821116 in the HLA-C and UBE2L3 genes and the effect of telbivudine antiviral therapy during pregnancy in HBeAg-positive mothers through a large-sample control study, and to provide a basis for the development of individualized blocking strategies for pregnant women with a high viral load. Methods: The genotypes of rs3130542 and rs4821116 were determined for 312 pregnant women with a high viral load who received telbivudine antiviral therapy during the second or third trimester of pregnancy, and the dominant model, recessive model, and additive model were used to analyze the association between the genotypes of these two loci and the reduction in HBV DNA load...
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Marybeth Carmody, Tara P Notarianni, Larissa A Sambel, Shannon J Walsh, Jenna M Burke, Jenna L Armstrong, T Glen Lawson
The encephalomyocarditis virus (EMCV) 3C protease (3Cpro ) is one of a small number of viral proteins whose concentration is known to be regulated by the cellular ubiquitin-proteasome system. Here we report that the ubiquitin-conjugating enzyme UbcH7/UBE2L3 and the ubiquitin-protein ligase E6AP/UBE3A are components of a previously unknown EMCV 3Cpro -polyubiquitylating pathway. Following the identification of UbcH7/UBE2L3 as a participant in 3Cpro ubiquitylation, we purified a UbcH7-dependent 3Cpro -ubiquitylating activity from mouse cells, which we identified as E6AP...
December 9, 2017: Biochemical and Biophysical Research Communications
Suwipa Ramphan, Sarawut Khongwichit, Chonticha Saisawang, Duangnapa Kovanich, Albert J Ketterman, Sukathida Ubol, Prasert Auewarakul, Sittiruk Roytrakul, Duncan R Smith, Atichat Kuadkitkan
PURPOSE: Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV nonstructural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes. EXPERIMENTAL DESIGN: To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2-pro) was transfected into Hela cells, and differential protein expression was detected by 2-dimension (2D) polyacrylamide gel electrophoresis...
October 4, 2017: Proteomics. Clinical Applications
Lizbeth Grimaldo, Alejandro Sandoval, Edgar Garza-López, Ricardo Felix
N-type calcium (CaV2.2) channels are widely expressed in the brain and the peripheral nervous system, where they play important roles in the regulation of transmitter release. Although CaV2.2 channel expression levels are precisely regulated, presently little is known regarding the molecules that mediate its synthesis and degradation. Previously, by using a combination of biochemical and functional analyses, we showed that the complex formed by the light chain 1 of the microtubule-associated protein 1B (LC1-MAP1B) and the ubiquitin-proteasome system (UPS) E2 enzyme UBE2L3, may interact with the CaV2...
2017: PloS One
Evanthia E Pashos, YoSon Park, Xiao Wang, Avanthi Raghavan, Wenli Yang, Deepti Abbey, Derek T Peters, Juan Arbelaez, Mayda Hernandez, Nicolas Kuperwasser, Wenjun Li, Zhaorui Lian, Ying Liu, Wenjian Lv, Stacey L Lytle-Gabbin, Dawn H Marchadier, Peter Rogov, Jianting Shi, Katherine J Slovik, Ioannis M Stylianou, Li Wang, Ruilan Yan, Xiaolan Zhang, Sekar Kathiresan, Stephen A Duncan, Tarjei S Mikkelsen, Edward E Morrisey, Daniel J Rader, Christopher D Brown, Kiran Musunuru
Genome-wide association studies have struggled to identify functional genes and variants underlying complex phenotypes. We recruited a multi-ethnic cohort of healthy volunteers (n = 91) and used their tissue to generate induced pluripotent stem cells (iPSCs) and hepatocyte-like cells (HLCs) for genome-wide mapping of expression quantitative trait loci (eQTLs) and allele-specific expression (ASE). We identified many eQTL genes (eGenes) not observed in the comparably sized Genotype-Tissue Expression project's human liver cohort (n = 96)...
April 6, 2017: Cell Stem Cell
H Mao, K Chen, X Zhu, Q Luo, J Zhao, W Li, X Wu, H Xu
A systematic study was conducted to identify reliable reference genes for normalization of gene expression analysis in the blotched snakehead Channa maculata under normal physiological conditions. Firstly, the partial complementary (c)DNA of nine candidate reference genes (actb, tmem104, ube2l3, ef1α, churc1, tmem256, rpl13a, sep15 and g6pd) were cloned from C. maculata. The expression levels of these genes were then assessed in embryos of different developmental stages and various tissue types of adult fish using quantitative real-time (qrt-)PCR...
June 2017: Journal of Fish Biology
Reetta Holmila, Athena Sklias, David C Muller, Davide Degli Esposti, Paule Guilloreau, James Mckay, Suleeporn Sangrajrang, Petcharin Srivatanakul, Pierre Hainaut, Philippe Merle, Zdenko Herceg, Andre Nogueira da Costa
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, but is still lacking sensitive and specific biomarkers for early diagnosis and prognosis. In this study, we applied targeted massively parallel semiconductor sequencing to assess methylation on a panel of genes (FBLN1, HINT2, LAMC1, LTBP1, LTBP2, PSMA2, PSMA7, PXDN, TGFB1, UBE2L3, VIM and YWHAZ) in plasma circulating cell-free DNA (cfDNA) and to evaluate the potential of these genes as HCC biomarkers in two different series, one from France (42 HCC cases and 42 controls) and one from Thailand (42 HCC cases, 26 chronic liver disease cases and 42 controls)...
2017: PloS One
Matthew J G Eldridge, Julia Sanchez-Garrido, Gil Ferreira Hoben, Philippa J Goddard, Avinash R Shenoy
Caspase-1 activation by inflammasome signaling scaffolds initiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-interleukin 1 beta (IL-1β) into its mature form and directs its secretion, triggering pyroptosis and release of non-substrate alarmins such as interleukin 1 alpha (IL-1α) and HMGB1. While some caspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here, we use unbiased proteomics to show that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1...
January 31, 2017: Cell Reports
Rhiannon R White, Amy H Ponsford, Michael P Weekes, Rachel B Rodrigues, David B Ascher, Marco Mol, Murray E Selkirk, Steven P Gygi, Christopher M Sanderson, Katerina Artavanis-Tsakonas
Trichinella spiralis is a muscle-specific parasitic worm that is uniquely intracellular. T. spiralis reprograms terminally differentiated skeletal muscle cells causing them to de-differentiate and re-enter the cell cycle, a process that cannot occur naturally in mammalian skeletal muscle cells, but one that holds great therapeutic potential. Although the host ubiquitin pathway is a common target for viruses and bacteria during infection, its role in parasite pathogenesis has been largely overlooked. Here we demonstrate that the secreted proteins of T...
November 2016: PLoS Pathogens
Arno F Alpi, Viduth Chaugule, Helen Walden
Ubiquitin signalling is a fundamental eukaryotic regulatory system, controlling diverse cellular functions. A cascade of E1, E2, and E3 enzymes is required for assembly of distinct signals, whereas an array of deubiquitinases and ubiquitin-binding modules edit, remove, and translate the signals. In the centre of this cascade sits the E2-conjugating enzyme, relaying activated ubiquitin from the E1 activating enzyme to the substrate, usually via an E3 ubiquitin ligase. Many disease states are associated with dysfunction of ubiquitin signalling, with the E3s being a particular focus...
October 15, 2016: Biochemical Journal
Simon Rothwell, Janine A Lamb, Hector Chinoy
PURPOSE OF REVIEW: This article reviews the advances that have been made in our understanding of the genetics of the idiopathic inflammatory myopathies (IIM) in the past 2 years, with a particular focus on polymyositis, dermatomyositis and inclusion body myositis. RECENT FINDINGS: Two large human leukocyte antigen (HLA) imputation studies have confirmed a strong association with the 8.1 ancestral haplotype in clinical subgroups of myositis and suggest multiple independent associations on this haplotype...
November 2016: Current Opinion in Rheumatology
Zhihua Wan, Xiaofang Lin, Tongyang Li, Aifen Zhou, Mei Yang, Dan Hu, Li Feng, Songxu Peng, Linlin Fan, Si Tu, Bin Zhang, Yukai Du
Intrauterine infection of hepatitis B virus (HBV), which accounts for the majority of mother-to-child transmission, is one of the main reasons for the failure of combined immunoprophylaxis against the transmission. Recent studies have identified that genetic background might influence the susceptibility to intrauterine infection of HBV. We conducted this study to investigate the associations between 10 genetic variants in 9 genes (SLC10A1, HLA-DP, HLA-C, CXCR5, CXCL13, TLR3, TLR4, TLR9 and UBE2L3) of mothers and their neonates and HBV intrauterine infection...
2016: Scientific Reports
Yu Wang, Yuan-feng Zhu, Qiong Wang, Jing Xu, Ni Yan, Jian Xu, Liang-feng Shi, Shuang-tao He, Jin-an Zhang
BACKGROUND: The ubiquitin conjugating enzyme E2L3 (UBE2L3) gene is associated with susceptibility to many autoimmune diseases. The aim of this study was to investigate the association between UBE2L3 gene and autoimmune thyroid diseases (AITDs) and their clinical phenotypes. METHODS: We genotyped five single-nucleotide polymorphisms (SNPs) rs131654, rs5754217, rs2298428, rs140489 and rs5998672 of UBE2L3 gene in case groups including 1028 patients with AITDs [676 cases of Graves' disease (GD) and 352 cases of Hashimoto's thyroiditis (HT)] and control group including 897 healthy individuals...
April 19, 2016: BMC Endocrine Disorders
Shilu Mathew, Hany Abdel-Hafiz, Abbas Raza, Kaneez Fatima, Ishtiaq Qadri
Hepatocellular carcinoma (HCC) is etiologically linked with hepatitis B virus (HBV) and is the leading cause of death amongst 80% of HBV patients. Among HBV affected patients, genetic factors are also involved in modifying the risk factors of HCC. However, the genetic factors that regulate progression to HCC still remain to be determined. In this review, we discuss several single nucleotide polymorphisms (SNPs) which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection such as cyclooxygenase (COX)-2 expression specifically at COX-2 -1195G/A in Chinese, Turkish and Egyptian populations, tumor necrosis factor α and the three most commonly studied SNPs: PAT-/+, Lys939Gln (A33512C, rs2228001) and Ala499Val (C21151T, rs2228000)...
April 8, 2016: World Journal of Hepatology
Otsanda Ruiz-Larrañaga, Paola Migliorini, Maria Uribarri, László Czirják, Maria C Alcaro, Jokin Del Amo, Mikel Iriondo, Carmen Manzano, Sergio Escorza-Treviño, Andone Estonba
Epidemiological studies suggest a strong contribution of genetic factors in the pathogenesis of systemic lupus erythematosus (SLE). In the last decades, many risk loci have been identified in several genetic association studies following both candidate gene and genome-wide approaches. The present work was conducted by GAPAID (Genes And Proteins for AutoImmunity Diagnostics) consortium with a dual aim: to replicate the association of several previously reported SLE susceptibility loci in an independent European sample and to explore their relation with some disease subphenotypes...
May 2016: Clinical Rheumatology
V Pascual, L M Medrano, N López-Palacios, A Bodas, B Dema, M Fernández-Arquero, B González-Pérez, I Salazar, C Núñez
Celiac disease (CD) is developed after gluten ingestion in genetically susceptible individuals. It can appear at any time in life, but some differences are commonly observed between individuals with onset early in life or in adulthood. We aimed to investigate the molecular basis underlying those differences. We collected 19 duodenal biopsies of children and adults with CD and compared the expression of 38 selected genes between each other and with the observed in 13 non-CD controls matched by age. A Bayesian methodology was used to analyze the differences of gene expression between groups...
2016: PloS One
Eunhee G Kim, Soo Heon Kwak, Daehee Hwang, Eugene C Yi, Kyong Soo Park, Bo Kyung Koo, Kristine M Kim
BACKGROUND: The prevalence of novel type 1 diabetes mellitus (T1DM) antibodies targeting eukaryote translation elongation factor 1 alpha 1 autoantibody (EEF1A1-AAb) and ubiquitin-conjugating enzyme 2L3 autoantibody (UBE2L3-AAb) has been shown to be negatively correlated with age in T1DM subjects. Therefore, we aimed to investigate whether age affects the levels of these two antibodies in nondiabetic subjects. METHODS: EEF1A1-AAb and UBE2L3-AAb levels in nondiabetic control subjects (n=150) and T1DM subjects (n=101) in various ranges of age (18 to 69 years) were measured using an enzyme-linked immunosorbent assay...
April 2016: Diabetes & Metabolism Journal
Yueting Shao, Daniel Figeys, Zhibin Ning, Ryan Mailloux, Hing Man Chan
Exposure to environmental chemicals has been implicated as a possible risk factor for the development of neurodegenerative diseases. Our previous study showed that methylmercury (MeHg) exposure can disrupt synthesis, uptake and metabolism of dopamine similar to 1-methyl-4-phenylpyridinium (MPP(+)). The objective of this study was to investigate the effects of MeHg exposure on gene and protein profiles in a dopaminergic MN9D cell line. MN9D cells were treated with MeHg (1-5 μM) and MPP(+) (10-40 μM) for 48 hr...
December 2015: Journal of Toxicological Sciences
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