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https://www.readbyqxmd.com/read/29453355/co-expression-network-analysis-and-cis-regulatory-element-enrichment-determine-putative-functions-and-regulatory-mechanisms-of-grapevine-atl-e3-ubiquitin-ligases
#1
Darren C J Wong, Pietro Ariani, Simone Castellarin, Annalisa Polverari, Elodie Vandelle
Arabidopsis thaliana Toxicos en Levadura (ATL) proteins are a subclass of the RING-H2 zinc finger binding E3 ubiquitin ligases. The grapevine (Vitis vinifera) ATL family was recently characterized, revealing 96 members that are likely to be involved in several physiological processes through protein ubiquitination. However, the final targets and biological functions of most ATL E3 ligases are still unknown. We analyzed the co-expression networks among grapevine ATL genes across a set of transcriptomic data related to defense and abiotic stress, combined with a condition-independent dataset...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29452935/e3-ligase-vhl-promotes-group-2-innate-lymphoid-cell-maturation-and-function-via-glycolysis-inhibition-and-induction-of-interleukin-33-receptor
#2
Qian Li, Dulei Li, Xian Zhang, Qingqing Wan, Wen Zhang, Mingke Zheng, Le Zou, Chris Elly, Jee H Lee, Yun-Cai Liu
Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition...
February 6, 2018: Immunity
https://www.readbyqxmd.com/read/29450633/mid1-pp2a-complex-functions-as-new-insights-in-human-lung-adenocarcinoma
#3
Lin Zhang, Junyao Li, Xuejiao Lv, Tingting Guo, Wei Li, Jie Zhang
PURPOSE: MID1 is an E3 ubiquitin ligase that was first found in Opitz G/BBB syndrome, but there has been little research into its role in lung diseases. We have found an accumulating evidence that indicates the MID1-PP2A complex plays a role in asthma and contributes to inflammation, but its roles in lung adenocarcinoma are unclear. This study aimed at evaluating the function of MID1-PP2A complex in human lung adenocarcinoma. METHODS: We used western blot, ELISA and real-time quantitative PCR to detect the protein and mRNA levels of MID1 and PP2A in A549, H1975, and H1650 lung adenocarcinoma cell lines compared with the human bronchial epithelial cell line BEAS-2B...
February 15, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29450620/targeting-the-neddylation-pathway-in-cells-as-a-potential-therapeutic-approach-for-diseases
#4
REVIEW
Jie Ying, Miaomiao Zhang, Xiaoyan Qiu, Yu Lu
The ubiquitin-proteasome system (UPS) is an important system that regulates the balance of intracellular proteins, and it is involved in the regulation of multiple vital biological processes. The approval of bortezomib for relapsed and refractory multiple myeloma has proven that agents targeting the UPS have the potential to be effective treatment strategies for diseases. Among of all of the components of the UPS, cullin-RING ligases (CRLs) are the focus of research. CRLs are the largest family of ubiquitin E3 ligases and they play a critical role in substrate binding...
February 15, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29449372/ligand-mediated-protein-degradation-reveals-functional-conservation-among-sequence-variants-of-the-cul4-type-e3-ligase-substrate-receptor-cereblon
#5
Afua A Akuffo, Aileen Y Alontaga, Rainer Metcalf, Matthew S Beatty, Andreas Becker, Jessica M McDaniel, Rebecca S Hesterberg, William E Goodheart, Steven Gunawan, Muhammad Ayaz, Yan Yang, Md Rezaul Karim, Morgan E Orobello, Kenyon Daniel, Wayne Guida, Jeffrey A Yoder, Anjali M Rajadhyaksha, Ernst Schonbrunn, Harshani R Lawrence, Nicholas J Lawrence, Pearlie K Epling-Burnette
Upon binding to thalidomide and other immunomodulatory drugs, the E3 ligase substrate receptor cereblon (CRBN) promotes proteasomal destruction by engaging the DDB1-CUL4A-Roc1-RBX1 E3-ubiquitin ligase in human cells but not in mouse cells suggesting that sequence variations in CRBN may cause its inactivation. Therapeutically, CRBN engagers have the potential for broad applications in cancer and immune therapy by specifically reducing protein expression through targeted ubiquitin-mediated degradation. To examine the effects of defined sequence changes on CRBNs activity, we performed a comprehensive study using complementary theoretical, biophysical, and biological assays aimed at understanding CRBNs non-primate sequence variations...
February 15, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29449217/zfp36l2-is-a-cell-cycle-regulated-ccch-protein-necessary-for-dna-lesion-induced-s-phase-arrest
#6
Aya Noguchi, Shungo Adachi, Naoto Yokota, Tomohisa Hatta, Tohru Natsume, Hiroyuki Kawahara
ZFP36L2 promotes the destruction of AU-rich element-containing transcripts, while its regulation and functional significance in cell cycle control are scarcely identified. We show that ZFP36L2 is a cell cycle-regulated CCCH protein whose abundance is regulated post-translationally at the respective stages of the cell cycle. Indeed, ZFP36L2 protein was eliminated after release from M phase, and ZYG11B-based E3 ligase plays a role in its polyubiquitination in interphase. Although ZFP36L2 is dispensable for normal cell cycle progression, we found that endogenous ZFP36L2 played a key role in cisplatin-induced S-phase arrest, a process in which the suppression of G1/S cyclins is necessary...
February 15, 2018: Biology Open
https://www.readbyqxmd.com/read/29447976/identification-of-a-novel-host-protein-sinal10-interacting-with-gp64-and-its-role-in-bombyx-mori-nucleopolyhedrovirus-infection
#7
Min Feng, Xiangshuo Kong, Jianjia Zhang, Weifan Xu, Xiaofeng Wu
Bombyx mori nucleopolyhedrovirus (BmNPV) is the most important pathogen of Bombyx mori, silkworm and causes severe losses in the silk industry. During the virus infectious cycle, budded virus (BVs) and occlusion-derived virus (ODVs) particles, which have identical genetic content but different phenotypes, are produced. The envelope glycoprotein GP64, specific in BVs, is involved in host cell receptor binding and is sufficient to mediate membrane fusion during the viral entry. However, the host cell factors, interacting with GP64 to mediate BVs infection, are still unknown...
February 12, 2018: Virus Research
https://www.readbyqxmd.com/read/29445227/novel-ubiquitin-independent-nucleolar-c-myc-degradation-pathway-mediated-by-antizyme-2
#8
Noriyuki Murai, Yasuko Murakami, Ayasa Tajima, Senya Matsufuji
The proto-oncogene c-Myc encodes a short-lived protein c-Myc that regulates various cellular processes including cell growth, differentiation and apoptosis. Degradation of c-Myc is catalyzed by the proteasome and requires phosphorylation of Thr-58 for ubiquitination by E3 ubiquitin ligase, Fbxw7/ FBW7. Here we show that a polyamine regulatory protein, antizyme 2 (AZ2), interacts with c-Myc in the nucleus and nucleolus, to accelerate proteasome-mediated c-Myc degradation without ubiquitination or Thr-58 phosphorylation...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445151/the-vesicle-trafficking-regulator-pn_scd1-is-demethylated-and-overexpressed-in-florets-of-apomictic-paspalum-notatum-genotypes
#9
Marika Bocchini, Giulio Galla, Fulvio Pupilli, Michele Bellucci, Gianni Barcaccia, Juan Pablo A Ortiz, Silvina C Pessino, Emidio Albertini
Apomixis (asexual reproduction through seeds) is considered a deviation of the sexual reproductive pathway leading to the development of clonal progenies genetically identical to the mother plant. Here we used the Methylation-Sensitive Amplification Polymorphism (MSAP) technique to characterize cytosine methylation patterns occurring in florets of sexual and aposporous Paspalum notatum genotypes, in order to identify epigenetically-controlled genes putatively involved in apomixis development. From twelve polymorphic MSAP-derived sequences, one (PN_6...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445034/the-skp1-cullin-f-box-e3-ligase-%C3%AE-trcp-and-cdk2-cooperate-to-control-stil-abundance-and-centriole-number
#10
Christian Arquint, Fabien Cubizolles, Agathe Morand, Alexander Schmidt, Erich A Nigg
Deregulation of centriole duplication has been implicated in cancer and primary microcephaly. Accordingly, it is important to understand how key centriole duplication factors are regulated. E3 ubiquitin ligases have been implicated in controlling the levels of several duplication factors, including PLK4, STIL and SAS-6, but the precise mechanisms ensuring centriole homeostasis remain to be fully understood. Here, we have combined proteomics approaches with the use of MLN4924, a generic inhibitor of SCF E3 ubiquitin ligases, to monitor changes in the cellular abundance of centriole duplication factors...
February 2018: Open Biology
https://www.readbyqxmd.com/read/29444369/rotaviral-non-structural-protein-4-triggers-dynamin-related-protein-1-dependent-mitochondrial-fragmentation-during-infection
#11
Arpita Mukherjee, Upayan Patra, Rahul Bhowmick, Mamta Chawla-Sarkar
Dynamic equilibrium between mitochondrial fission and mitochondrial fusion serves as an important quality control system within cells ensuring cellular vitality and homeostasis. Viruses often target mitochondrial dynamics as a part of their obligatory cellular reprogramming. The present study was undertaken to assess the status and regulation of mitochondrial dynamics during rotavirus (RV) infection. Distinct fragmentation of mitochondrial syncytia was observed during late hours of RV (SA11, Wa, A5-13) infection...
February 14, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29443041/in-vitro-sumoylation-assay-to-study-sumo-e3-ligase-activity
#12
Wan-Shan Yang, Mel Campbell, Hsing-Jien Kung, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification is an important post-translational modification (PTM) that mediates signal transduction primarily through modulating protein-protein interactions. Similar to ubiquitin modification, SUMOylation is directed by a sequential enzyme cascade including E1-activating enzyme (SAE1/SAE2), E2-conjugation enzyme (Ubc9), and E3-ligase (i.e., PIAS family, RanBP2, and Pc2). However, different from ubiquitination, an E3 ligase is non-essential for the reaction but does provide precision and efficacy for SUMO conjugation...
January 29, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29441057/stability-of-the-htlv-1-antisense-derived-protein-hbz-is-regulated-by-the-e3-ubiquitin-protein-ligase-ubr5
#13
Amanda R Panfil, Jacob Al-Saleem, Cory M Howard, Nikoloz Shkriabai, Mamuka Kvaratskhelia, Patrick L Green
Human T-cell leukemia virus type 1 (HTLV-1) encodes a protein derived from the antisense strand of the proviral genome designated HBZ (HTLV-1 basic leucine zipper factor). HBZ is the only viral gene consistently expressed in infected patients and adult T-cell leukemia/lymphoma (ATL) tumor cell lines. It functions to antagonize many activities of the Tax viral transcriptional activator, suppresses apoptosis, and supports proliferation of ATL cells. Factors that regulate the stability of HBZ are thus important to the pathophysiology of ATL development...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29440269/the-mtdmi2-mtpub2-negative-feedback-loop-plays-a-role-in-nodulation-homeostasis
#14
Jiaxing Liu, Jie Deng, Fugui Zhu, Yuan Li, Zheng Lu, Peibin Qin, Tao Wang, Jiangli Dong
MtDMI2 is a leucine-rich repeat (LRR)-type receptor kinase required for the signal transduction in the symbiosis pathway. However, the mechanisms through which MtDMI2 participates in nodulation homeostasis are poorly understood. In this study, we identified MtPUB2, a new plant U-box (PUB)-type E3 ligase, and showed that it interacts with MtDMI2. The expression pattern of these proteins is similar in various tissues. MtPUB2-RNAi roots exhibit impaired infection threads, fewer nodules, and shorter primary root length compared with empty vector-transformed plants...
February 13, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29438996/global-identification-of-sumo-substrates-reveals-crosstalk-between-sumoylation-and-phosphorylation-promotes-cell-migration
#15
Ijeoma Uzoma, Jianfei Hu, Eric Cox, Shuli Xia, Jianying Zhou, Hee-Sool Rho, Catherine Guzzo, Corry Paul, Olutobi Ajala, C Rory Goodwin, Junseop Jeong, Cedric Moore, Hui Zhang, Pamela Meluh, Seth Blackshaw, Michael Matunis, Jiang Qian, Heng Zhu
Proteomics studies have revealed that SUMOylation is widely used posttranslational modification (PTM) in eukaryotes. However, how SUMO E1/2/3 complexes use different SUMO isoforms and recognize substrates remains largely unknown.  Using a human proteome microarray-based activity screen, we identified over 2,500 proteins that undergo SUMO E3-dependent SUMOylation.  We next constructed a SUMO isoform- and E3 ligase-dependent enzyme-substrate relationship network. Protein kinases were significantly enriched among SUMOylation substrates, suggesting crosstalk between tyrosine phosphorylation and SUMOylation...
February 8, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29438012/hedgehog-reciprocally-controls-trafficking-of-smo-and-ptc-through-the-smurf-family-of-e3-ubiquitin-ligases
#16
Shuang Li, Shuangxi Li, Bing Wang, Jin Jiang
Hedgehog (Hh) induces signaling by promoting the reciprocal trafficking of its receptor Patched (Ptc) and the signal transducer Smoothened (Smo), which is inhibited by Ptc, at the cell surface. We identified Smurf family E3 ubiquitin ligases as essential for Smo ubiquitylation and cell surface clearance and demonstrated that Smurf family members mediate the reciprocal trafficking of Ptc and Smo in Drosophila melanogaster G protein-coupled receptor kinase 2 (Gprk2)-mediated phosphorylation of Smurf promoted Smo ubiquitylation by increasing the recruitment of Smurf to Smo, whereas protein kinase A (PKA)-mediated phosphorylation of Smo caused Smurf to dissociate from Smo, thereby inhibiting Smo ubiquitylation...
February 6, 2018: Science Signaling
https://www.readbyqxmd.com/read/29435596/ripk4-activity-in-keratinocytes-is-controlled-by-the-scf%C3%AE-trcp-ubiquitin-ligase-to-maintain-cortical-actin-organization
#17
Giel Tanghe, Corinne Urwyler-Rösselet, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, Wim Declercq
RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state...
February 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29435413/the-e3-ubiquitin-ligase-murf2-attenuates-lps-induced-macrophage-activation-by-inhibiting-production-of-inflammatory-cytokines-and-migration
#18
Hongjun Bian, Shanshan Gao, Di Zhang, Qi Zhao, Feifei Li, Xiao Li, Shuohuan Sun, Shouyang Song, Tao Li, Qiang Zhu, Wanhua Ren, Chengyong Qin, Jianni Qi
Muscle RING-finger (MuRF) proteins are E3 ubiquitin ligases that are expressed in striated muscle. MuRF2 is an important member of this family, but whether it is expressed in tissues other than striated muscle has not been thoroughly elucidated to date. In this study, we determined that MuRF2 is also expressed in other vital organs, including liver, lung, brain, spleen and kidney. Moreover, we show that the level of MuRF2 expression is significantly decreased in hepatic mononuclear cells of mice with lipopolysaccharide (LPS)/d-galactosamine-induced hepatitis and negatively correlated with the serum levels of alanine aminotransferase and aspartate aminotransferase in these mice...
February 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29435114/ras-gtpases-are-modified-by-sumoylation
#19
Byeong Hyeok Choi, Changyan Chen, Mark Philips, Wei Dai
RAS proteins are GTPases that participate in multiple signal cascades, regulating crucial cellular processes including cell survival, proliferation, differentiation, and autophagy. Mutations or deregulated activities of RAS are frequently the driving force for oncogenic transformation and tumorigenesis. Given the important roles of the small ubiquitin-related modifier (SUMO) pathway in controlling the stability, activity, or subcellular localization of key cellular regulators, we investigated here whether RAS proteins are posttranslationally modified (i...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435015/phosphoproteomic-analysis-of-the-antitumor-effects-of-ginsenoside-rg3-in-human-breast-cancer-cells
#20
Mingjin Zou, Jing Wang, Jidong Gao, Hui Han, Yi Fang
The incidence of breast cancer has been increasing in China and the age of breast cancer onset is earlier compared with Western countries. Compounds commonly used in Traditional Chinese Medicine (TCM) are an important source of anticancer drugs. Ginseng is one of the most common medicines used in TCM. Ginsenosides, which are saponins found in the ginseng plant, are the major active components responsible for the chemopreventive effects of ginseng in cancer. However, the mechanisms by which ginsenosides exert their anticancer effects remain elusive...
March 2018: Oncology Letters
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