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Ubiquitination

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https://www.readbyqxmd.com/read/28918480/sgs1-helicase-is-required-for-efficient-pcna-monoubiquitination-and-translesion-dna-synthesis-in-saccharomyces-cerevisiae
#1
Fangfang Li, Lindsay G Ball, Li Fan, Michelle Hanna, Wei Xiao
DNA-damage tolerance (DDT) is employed by eukaryotes to deal with replication blocks on the template strand, and is divided into two parallel pathways that are activated by sequential ubiquitination of proliferating cell nuclear antigen (PCNA) at the Lys164 residue. Rad6-Rad18-mediated PCNA monoubiquitination promotes translesion DNA synthesis (TLS) and the monoubiquitinated PCNA can be further polyubiquitinated by an Mms2-Ubc13-Rad5 complex, leading to error-free lesion bypass. We previously reported that the DNA helicase Sgs1 is required for error-free lesion bypass, probably through the double-Holliday junction migration and subsequent resolution...
September 16, 2017: Current Genetics
https://www.readbyqxmd.com/read/28918148/mammalian-target-of-rapamycin-signaling-and-ubiquitin-proteasome-related-gene-expression-in-3-different-skeletal-muscles-of-colostrum-versus-formula-fed-calves
#2
H Sadri, J Steinhoff-Wagner, Harald M Hammon, R M Bruckmaier, S Görs, H Sauerwein
The rates of protein turnover are higher during the neonatal period than at any other time in postnatal life. The mammalian target of rapamycin (mTOR) and the ubiquitin-proteasome system are key pathways regulating cellular protein turnover. The objectives of this study were (1) to elucidate the effect of feeding colostrum versus milk-based formula on the mRNA abundance of key components of the mTOR pathway and of the ubiquitin-proteasome system in skeletal muscle of neonatal calves and (2) to compare different muscles...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28918024/antisense-oligonucleotide-mediated-removal-of-the-polyglutamine-repeat-in-spinocerebellar-ataxia-type-3-mice
#3
Lodewijk J A Toonen, Frank Rigo, Haico van Attikum, Willeke M C van Roon-Mom
Spinocerebellar ataxia type 3 (SCA3) is a currently incurable neurodegenerative disorder caused by a CAG triplet expansion in exon 10 of the ATXN3 gene. The resultant expanded polyglutamine stretch in the mutant ataxin-3 protein causes a gain of toxic function, which eventually leads to neurodegeneration. One important function of ataxin-3 is its involvement in the proteasomal protein degradation pathway, and long-term downregulation of the protein may therefore not be desirable. In the current study, we made use of antisense oligonucleotides to mask predicted exonic splicing signals, resulting in exon 10 skipping from ATXN3 pre-mRNA...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917607/selection-of-reliable-reference-genes-for-gene-expression-studies-in-botrytis-cinerea
#4
He Ren, Xiaoqing Wu, Yuping Lyu, Hongzi Zhou, Xueying Xie, Xinjian Zhang, Hetong Yang
Botrytis cinerea is an important plant pathogen causing grey mold disease in a wide range of plant species. The aim of this study was to identify reliable reference genes that can be used for the analysis of relative gene expression in B. cinerea with quantitative real-time reverse transcription PCR (qRT-PCR). Six commonly used housekeeping genes including actin (ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), ubiquitin (UBQ), ubiquitin-conjugating enzyme (UCE), α-tubulin (α-TUB) and β-tubulin (β-TUB) were selected to test their expression stabilities in B...
September 13, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28916785/selective-degradation-of-pu-1-during-autophagy-represses-the-differentiation-and-antitumour-activity-of-th9-cells
#5
Thaiz Rivera Vargas, Zhijian Cai, Yingying Shen, Magalie Dosset, Isis Benoit-Lizon, Tiffany Martin, Aurélie Roussey, Richard A Flavell, François Ghiringhelli, Lionel Apetoh
Autophagy, a catabolic mechanism that involves degradation of cellular components, is essential for cell homeostasis. Although autophagy favours the lineage stability of regulatory T cells, the contribution of autophagy to the differentiation of effector CD4 T cells remains unclear. Here we show that autophagy selectively represses T helper 9 (TH9) cell differentiation. CD4 T cells lacking Atg3 or Atg5 have increased interleukin-9 (IL-9) expression upon differentiation into TH9 cells relative to Atg3- or Atg5-expressing control cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916745/cadmium-effects-on-dna-and-protein-metabolism-in-oyster-crassostrea-gigas-revealed-by-proteomic-analyses
#6
Jie Meng, Wenxiong Wang, Li Li, Qi Yin, Guofan Zhang
Marine molluscs, including oysters, can concentrate high levels of cadmium (Cd) in their soft tissues, but the molecular mechanisms of Cd toxicity remain speculative. In this study, Pacific oysters (Crassostrea gigas) were exposed to Cd for 9 days and their gills were subjected to proteomic analysis, which were further confirmed with transcriptomic analysis. A total of 4,964 proteins was quantified and 515 differentially expressed proteins were identified in response to Cd exposure. Gene Ontology enrichment analysis revealed that excess Cd affected the DNA and protein metabolism...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28916538/analysis-of-blood-based-gene-expression-in-idiopathic-parkinson-disease
#7
Ron Shamir, Christine Klein, David Amar, Eva-Juliane Vollstedt, Michael Bonin, Marija Usenovic, Yvette C Wong, Ales Maver, Sven Poths, Hershel Safer, Jean-Christophe Corvol, Suzanne Lesage, Ofer Lavi, Günther Deuschl, Gregor Kuhlenbaeumer, Heike Pawlack, Igor Ulitsky, Meike Kasten, Olaf Riess, Alexis Brice, Borut Peterlin, Dimitri Krainc
OBJECTIVE: To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). METHODS: Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature...
September 15, 2017: Neurology
https://www.readbyqxmd.com/read/28916376/transcriptome-profiling-of-the-plutella-xylostella-lepidoptera-plutellidae-ovary-reveals-genes-involved-in-oogenesis
#8
Lu Peng, Lei Wang, Yi-Fan Yang, Ming-Min Zou, Wei-Yi He, Yue Wang, Qing Wang, Liette Vasseur, Min-Sheng You
BACKGROUND: As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops...
September 12, 2017: Gene
https://www.readbyqxmd.com/read/28915662/cbl-b-predicts-postoperative-survival-in-patients-with-resectable-pancreatic-ductal-adenocarcinoma
#9
Qian Dong, Yuteng Ma, Yao Zhang, Xiujuan Qu, Zhi Li, Yafei Qi, Yunpeng Liu, Ce Li, Kai Li, Xianghong Yang, Xiaofang Che
Casitas B-lineage lymphoma b (Cbl-b) is a ubiquitin-protein ligase and a signal transducing adaptor protein involved in immune regulation, and it may be involved in the development and progression of cancer. We investigated the association between Cbl-b expression and prognosis in patients with resectable pancreatic ductal adenocarcinoma (PDAC). The clinicopathological characteristics and survival data of 134 patients with surgery for PDAC between January 2009 and February 2012 were retrospectively evaluated, and Cbl-b expression was assayed by immunohistochemical staining...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915644/phytoagent-deoxyelephantopin-derivative-inhibits-triple-negative-breast-cancer-cell-activity-by-inducing-oxidative-stress-mediated-paraptosis-like-cell-death
#10
Jeng-Yuan Shiau, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
Triple negative breast cancer (TNBC) is a highly metastatic cancer among the breast cancer subgroups. A thorny issue for clinical therapy of TNBC is lack of an efficient targeted therapeutic strategy. We previously created a novel sesquiterpene lactone analog (named DETD-35) derived from plant deoxyelephantopin (DET) which exhibits potent effects against human TNBC MDA-MB-231 tumor growth in a xenograft mouse model. Here we studied the mechanisms of both DET and DETD-35 against MDA-MB-231 cells. DETD-35 (3-fold decreased in IC50) exhibited better anti-TNBC cell activity than DET as observed through induction of reactive oxygen species production (within 2 h treatment) and damage to the ER structures, resulting in ER-derived cytoplasmic vacuolation and ubiquitinated protein accumulation in the treated cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915616/tdp-43-hdac6-axis-promoted-tumor-progression-and-regulated-nutrient-deprivation-induced-autophagy-in-glioblastoma
#11
Tzu-Wei Lin, Ming-Teh Chen, Liang-Ting Lin, Pin-I Huang, Wen-Liang Lo, Yi-Ping Yang, Kai-Hsi Lu, Yi-Wei Chen, Shih-Hwa Chiou, Cheng-Wen Wu
Glioblastoma Multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. Surgical resection of GBM is greatly limited due to the biological significance of brain, giving rise to tumor relapse in GBM patients. Transactive response DNA binding protein-43 (TDP-43) is a DNA/RNA-binding protein known for causing neurodegenerative diseases through post-translational modification; but little is known about its involvement in cancer development. In this study, we found that nutrient deprivation in GBM cell lines elevated TDP-43 expression by a mechanism of evasion from ubiquitin-dependent proteolytic pathway, and subsequently activated the autophagy process...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915613/alternative-promotion-and-suppression-of-metastasis-by-jnk2-governed-by-its-phosphorylation
#12
Sike Hu, Xiaoli Dong, Wenjuan Gao, Dwayne Stupack, Yanhua Liu, Rong Xiang, Na Li
Fos-related antigen 1 (Fra1) has been proposed as a gatekeeper of the mesenchymal-epithelial transition to epithelial-mesenchymal transition. Here, we showed that de-phosphorylated JNK2 increased the expression of Fra1 by promoting the expression of c-Jun and Jun-B. Conversely, phosphorylated JNK2 suppressed its expression via enhancing the ubiquitination of c-Jun and Jun-B. These data provided insights into the regulatory mechanism of JNK2 on the expression of Fra1. Our study thus demonstrated that the conversion of JNK2 from its phosphorylation to de-phosphorylation status promoted the switch of breast cancer cells from mesenchymal-epithelial transition to epithelial-mesenchymal transition...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912474/rhus-coriaria-increases-protein-ubiquitination-proteasomal-degradation-and-triggers-non-canonical-beclin-1-independent-autophagy-and-apoptotic-cell-death-in-colon-cancer-cells
#13
Khawlah Athamneh, Hussain El Hasasna, Halima Al Samri, Samir Attoub, Kholoud Arafat, Nehla Benhalilou, Asma Al Rashedi, Yusra Al Dhaheri, Synan AbuQamar, Ali Eid, Rabah Iratni
Colorectal cancer is the fourth leading cause of cancer-related deaths worldwide. Here, we investigated the anticancer effect of Rhus coriaria extract (RCE) on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE significantly inhibited the viability and colony growth of colon cancer cells. Moreover, RCE induced Beclin-1-independent autophagy and subsequent caspase-7-dependent apoptosis. Blocking of autophagy by chloroquine significantly reduced RCE-induced cell death, while blocking of apoptosis had no effect on RCE-induced cell death...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912452/endogenous-%C3%AF-3-fatty-acid-production-by-fat-1-transgene-and-topically-applied-docosahexaenoic-acid-protect-against-uvb-induced-mouse-skin-carcinogenesis
#14
Hye-Won Yum, Jin Park, Hyun-Jung Park, Jun Wan Shin, Yong-Yeon Cho, Su-Jung Kim, Jing X Kang, Young-Joon Surh
The present study was intended to explore the effects of endogenously produced ω-3 polyunsaturated fatty acids (PUFAs) on ultraviolet B (UVB)-induced skin inflammation and photocarcinogenesis using hairless fat-1 transgenic mice harboring ω-3 desaturase gene capable of converting ω-6 to ω-3 PUFAs. Upon exposure to UVB irradiation, fat-1 transgenic mice exhibited a significantly reduced epidermal hyperplasia, oxidative skin damage, and photocarcinogenesis as compared to wild type mice. The transcription factor, Nrf2 is a master regulator of anti-inflammatory and antioxidant gene expression...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911847/analysis-of-structural-features-contributing-to-weak-affinities-of-ubiquitin-protein-interactions
#15
REVIEW
Ariel Cohen, Eran Rosenthal, Julia M Shifman
Ubiquitin is a small protein that enables one of the most common post-translational modifications, where the whole ubiquitin molecule is attached to various target proteins, forming mono- or polyubiquitin conjugations. As a prototypical multispecific protein, ubiquitin interacts non-covalently with a variety of proteins in the cell, including ubiquitin modifying enzymes and ubiquitin receptors that recognize signals from ubiquitin-conjugated substrates. To enable recognition of multiple targets and to support fast dissociation from the ubiquitin modifying enzymes, ubiquitin/protein interactions are characterized with low affinities, frequently in the higher μM and lower mM range...
September 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28911826/immunoproteasome-selective-and-non-selective-inhibitors-a-promising-approach-for-the-treatment-of-multiple-myeloma
#16
REVIEW
Roberta Ettari, Maria Zappalà, Silvana Grasso, Caterina Musolino, Vanessa Innao, Alessandro Allegra
The ubiquitin-proteasome system (UPS) is the major non-lysosomal proteolytic system for the degradation of abnormal or damaged proteins no longer required. The proteasome is involved in degradation of numerous proteins which regulate the cell cycle, indicating a role in controlling cell proliferation and maintaining cell survival. Defects in the UPS can lead to anarchic cell proliferation and to tumor development. For these reasons UPS inhibition has become a significant new strategy for drug development in cancer treatment...
September 11, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28911816/lead-discovery-and-chemical-biology-approaches-targeting-the-ubiquitin-proteasome-system
#17
REVIEW
Favour A Akinjiyan, Seth Carbonneau, Nathan T Ross
Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches...
August 30, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28911210/a20-an-essential-component-of-the-ubiquitin-editing-protein-complex-is-a-negative-regulator-of-inflammation-in-human-myometrium-and-foetal-membranes
#18
Martha Lappas
STUDY QUESTION: Does A20 regulate mediators involved in the terminal processes of human labour in primary myometrial and amnion cells? SUMMARY ANSWER: A20 is a nuclear factor-kappa B (NF-κB) responsive gene that acts as a negative regulator of NF-κB-induced expression of pro-labour mediators. WHAT IS KNOWN ALREADY: Inflammation is commonly implicated in spontaneous preterm birth and the processes involved in rupture of foetal membranes and uterine contractions...
September 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28910856/high-throughput-screening-of-hect-e3-ubiquitin-ligases-using-ubfluor
#19
Peter K Foote, David T Krist, Alexander V Statsyuk
HECT E3 ubiquitin ligases are responsible for many human disease phenotypes and are promising drug targets; however, screening assays for HECT E3 inhibitors are inherently complex, requiring upstream E1 and E2 enzymes as well as ubiquitin, ATP, and detection reagents. Intermediate ubiquitin thioesters and a complex mixture of polyubiquitin products provide further opportunities for off-target inhibition and increase the complexity of the assay. UbFluor is a novel ubiquitin thioester that bypasses the E1 and E2 enzymes and undergoes direct transthiolation with HECT E3 ligases...
September 14, 2017: Current Protocols in Chemical Biology
https://www.readbyqxmd.com/read/28910640/the-ubiquitin-ligase-smurf1-functions-in-selective-autophagy-of-mycobacterium-tuberculosis-and-anti-tuberculous-host-defense
#20
Luis H Franco, Vidhya R Nair, Caitlyn R Scharn, Ramnik J Xavier, Jose R Torrealba, Michael U Shiloh, Beth Levine
No abstract text is available yet for this article.
September 13, 2017: Cell Host & Microbe
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