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https://www.readbyqxmd.com/read/28643728/regulation-of-various-dna-repair-pathways-by-e3-ubiquitin-ligases
#1
REVIEW
Chandramouli Natarajan, Kenichi Takeda
DNA repair is the most important mechanism to maintain the normal cellular homeostasis. Owing to its complicated network, series of posttranslation modifications is required for proper function of the DNA repair proteins. One of such important posttranslation modifications is ubiquitination (attachment of ubiquitin). E3 ubiquitin ligases (UBLs) are a group of proteins that transfer ubiquitin from E2 conjugating enzymes to highly specific substrates such as DNA repair proteins. In this review, we have updated the role of different E3 UBL and how it regulates different DNA repair pathways...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28642478/a-novel-plant-e3-ligase-stabilizes-escherichia-coli-heat-shock-factor-%C3%AF-32
#2
Yulong Niu, Xibing Xu, Chengcheng Liu, Tao Wang, Ke Liang, Jianmei Wang, Zhibin Liu, Xufeng Li, Yi Yang
The heat shock response is crucial for organisms against heat-damaged proteins and maintaining homeostasis at a high temperature. Heterologous expression of eukaryotic molecular chaperones protects Escherichia coli from heat stress. Here we report that expression of the plant E3 ligase BnTR1 significantly increases the thermotolerance of E. coli. Different from eukaryotic chaperones, BnTR1 expression induces the accumulation of heat shock factor σ(32) and heat shock proteins. The active site of BnTR1 in E...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28639696/modulation-of-global-sumoylation-by-kaposi-s-sarcoma-associated-herpesvirus-and-its-effects-on-viral-gene-expression
#3
Jinzhong Wang, Yuying Guo, Xu Wang, Rui Zhao, Ying Wang
Some viruses have evolved to exploit the host SUMOylation system to regulate their own replication. Kaposi's sarcoma-associated herpesvirus (KSHV) encodes K-bZIP, a SUMO E3 ligase catalyzing the SUMOylation of viral and host proteins. KSHV also encodes replication and transcriptional activator (RTA), a SUMO-targeted ubiquitin ligase catalyzing the ubiquitination of SUMOylated proteins and targeting them for degradation. Using chronic KSHV-infected TRE × BCBL-1 RTA cells, the expression kinetics of K-bZIP and RTA, and the global SUMOylation level were detected...
June 22, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28638054/drug-repositioning-screening-for-keap1-nrf2-binding-inhibitors-using-fluorescence-correlation-spectroscopy
#4
Yuki Yoshizaki, Takayasu Mori, Mari Ishigami-Yuasa, Eriko Kikuchi, Daiei Takahashi, Moko Zeniya, Naohiro Nomura, Yutaro Mori, Yuya Araki, Fumiaki Ando, Shintaro Mandai, Yuri Kasagi, Yohei Arai, Emi Sasaki, Sayaka Yoshida, Hiroyuki Kagechika, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
The Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. The Cul3/Keap1 E3 ubiquitin ligase complex interacts with Nrf2, leading to Nrf2 ubiquitination and degradation. In this study, we focused on the disruption of the Keap1-Nrf2 interaction to upregulate Nrf2 expression and the transcription of ARE-controlled cytoprotective oxidative stress response enzymes, such as HO-1...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28636940/hectd3-mediates-an-hsp90-dependent-degradation-pathway-for-protein-kinase-clients
#5
Zhaobo Li, Lihong Zhou, Chrisostomos Prodromou, Velibor Savic, Laurence H Pearl
Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiquitylation is not understood, and the E3 ubiquitin ligases involved are largely unknown. Using a siRNA screen, we have identified components of two independent degradation pathways for the HSP90 client kinase CRAF...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#6
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630798/the-role-of-cullin4b-in-human-cancers
#7
REVIEW
Ying Li, Xin Wang
Cullin 4B (CUL4B) is a scaffold of the Cullin4B-Ring E3 ligase complex (CRL4B) that plays an important role in proteolysis and is implicated in tumorigenesis. Aberrant expression of CUL4B has been reported in various types of human diseases. Recently, studies have shown that CUL4B was overexpressed in a multitude of solid neoplasms and affect the expression of several tumor suppressor genes. In this review, we aim to summarize the biological function of CUL4B in order to better understand its pathogenesis in human cancers...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28630323/role-of-the-cbp-catalytic-core-in-intramolecular-sumoylation-and-control-of-histone-h3-acetylation
#8
Sangho Park, Robyn L Stanfield, Maria A Martinez-Yamout, H Jane Dyson, Ian A Wilson, Peter E Wright
The histone acetyl transferases CREB-binding protein (CBP) and its paralog p300 play a critical role in numerous cellular processes. Dysregulation of their catalytic activity is associated with several human diseases. Previous work has elucidated the regulatory mechanisms of p300 acetyltransferase activity, but it is not known whether CBP activity is controlled similarly. Here, we present the crystal structure of the CBP catalytic core encompassing the bromodomain (BRD), CH2 (comprising PHD and RING), HAT, and ZZ domains at 2...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630068/ehrlichia-chaffeensis-trp120-moonlights-as-a-hect-e3-ligase-involved-in-self-and-host-ubiquitination-to-influence-protein-interactions-and-stability-for-intracellular-survival
#9
Bing Zhu, Seema Das, Shubhajit Mitra, Tierra R Farris, Jere W McBride
Ehrlichia chaffeensis secretes tandem repeat protein (TRP) effectors that are involved in a diverse array of host cell interactions, some of which directly activate cell signaling pathways, and reprogram host gene transcription to promote survival in the mononuclear phagocyte. However, the molecular details of these effector-host interactions and roles in pathobiology are incompletely understood. In this study, we determined that the E. chaffeensis effector, TRP120, is post-translationally modified by ubiquitin (Ub), and ubiquitination occurs through intrinsic and host-mediated HECT ligase activity...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28628628/transcriptional-mechanisms-associated-with-seed-dormancy-and-dormancy-loss-in-the-gibberellin-insensitive-sly1-2-mutant-of-arabidopsis-thaliana
#10
Sven K Nelson, Camille M Steber
While widespread transcriptome changes were previously observed with seed dormancy loss, this study specifically characterized transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive sleepy1-2 (sly1-2) mutant. The SLY1 gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. DELLA overaccumulation in sly1-2 seeds leads to increased dormancy that can be rescued without DELLA protein destruction either by overexpression of the GA receptor, GA-INSENSITIVE DWARF1b (GID1b-OE) (74% germination) or by extended dry after-ripening (11 months, 51% germination)...
2017: PloS One
https://www.readbyqxmd.com/read/28628358/h2b-ubiquitination-conserved-molecular-mechanism-diverse-physiologic-functions-of-the-e3-ligase-during-meiosis
#11
Liying Wang, Cunwei Cao, Fang Wang, Jianguo Zhao, Wei Li
RNF20/Bre1 mediated H2B ubiquitination (H2Bub) has various physiologic functions. Recently, we found that H2Bub participates in meiotic recombination by promoting chromatin relaxation during meiosis. We then analyzed the phylogenetic relationships among the E3 ligase for H2Bub, its E2 Rad6 and their partner WW domain-containing adaptor with a coiled-coil (WAC) or Lge1, and found that the molecular mechanism underlying H2Bub is evolutionarily conserved from yeast to mammals. However, RNF20 has diverse physiologic functions in different organisms, which might be caused by the evolutionary divergency of their domain/motif architectures...
June 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28627598/curcumin-exerts-its-tumor-suppressive-function-via-inhibition-of-nedd4-oncoprotein-in-glioma-cancer-cells
#12
Xue Wang, Jiaojiao Deng, Jinxia Yuan, Xin Tang, Yuelong Wang, Haifeng Chen, Yi Liu, Liangxue Zhou
Glioblastoma is the most common brain cancer in adults. It represents one of the top ten malignant tumors with an average survival time of nine months despite treatments with surgery, radiotherapy and chemotherapy. Curcumin is a phytochemical turmeric isolated from root of the Curcuma longa plant. Accumulating evidence have proved that curcumin targets numerous cancer signaling pathways. The E3 ubiquitin ligase NEDD4, neural precursor cell expressed developmentally downregulated protein 4, is frequently overexpressed in various cancers...
June 8, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28626083/cellular-and-disease-functions-of-the-prader-willi-syndrome-gene-magel2
#13
REVIEW
Klementina Fon Tacer, Patrick Ryan Potts
Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme...
June 16, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28626006/atairp2-e3-ligase-affects-aba-and-high-salinity-responses-by-stimulating-its-atp1-sdirip1-substrate-turnover
#14
Tae Rin Oh, Jong Hum Kim, Seok Keun Cho, Moon Young Ryu, Seong Wook Yang, Woo Taek Kim
AtAIRP2 is a cytosolic RING-type E3 ubiquitin (Ub) ligase that positively regulates an ABA response in Arabidopsis (Arabidopsis thaliana). Yeast two-hybrid screening using AtAIRP2 as bait identified ATP1 (AtAIRP2 Target Protein 1) as a substrate of AtAIRP2. ATP1 was found to be identical to SDIRIP1, which was recently reported to be a negative factor in ABA signaling and a target protein of the RING E3 ligase SDIR1. ATP1 was accordingly renamed ATP1/SDIRIP1. A specific interaction between AtAIRP2 and ATP1/SDIRIP1 and ubiquitination of ATP1/SDIRIP1 by AtAIRP2 were demonstrated in vitro and in planta...
June 16, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28625874/negative-regulation-of-the-rlh-signaling-by-the-e3-ubiquitin-ligase-rnf114
#15
Boren Lin, Qi Ke, Haiying Li, Nichole S Pheifer, David C Velliquette, Douglas W Leaman
The retinoic acid-inducible gene-I (RIG-I)-like helicases (RLH)s are cytoplasmic pattern recognition receptors expressed in both immune and non-immune cells that are essential for detection of intracellular RNA products, primarily of viral origin. Upon binding to viral RNA, RLHs interact with mitochondrial antiviral signaling protein (MAVS) to activate interferon (IFN)-mediated antiviral responses. The RLH/MAVS signaling pathway is regulated by ubiquitination/deubiquitination, in which several ubiquitin-editing proteins play critical roles...
June 15, 2017: Cytokine
https://www.readbyqxmd.com/read/28625848/regulation-of-e2s-a-role-for-additional-ubiquitin-binding-sites
#16
REVIEW
Adam J Middleton, Joshua D Wright, Catherine L Day
Attachment of ubiquitin to proteins relies on a sophisticated enzyme cascade that is tightly regulated. The machinery of ubiquitylation responds to a range of signals, which remarkably includes ubiquitin itself. Thus ubiquitin is not only the central player in the ubiquitylation cascade, but also a key regulator. The ubiquitin E3 ligases provide specificity to the cascade and often bind the substrate, while the ubiquitin-conjugating enzymes (E2s) have a pivotal role in determining chain linkage and length. Interaction of ubiquitin with the E2 is important for activity, but the low affinity of these interactions has made them hard to identify and study...
June 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28623141/sirtuin-7-dependent-deacetylation-of-ddb1-regulates-the-expression-of-nuclear-receptor-tr4
#17
Md Fazlul Karim, Tatsuya Yoshizawa, Shihab U Sobuz, Yoshifumi Sato, Kazuya Yamagata
Sirtuin 7 (SIRT7) is an NAD(+)-dependent deacetylase/deacylase, but only a limited number of SIRT7 substrates have been identified. Recently, we found that Sirt7 knockout mice are resistant to high-fat diet-induced fatty liver, and that SIRT7 positively regulates the protein level of TR4, a nuclear receptor involved in lipid metabolism, by inhibiting the CUL4B/DDB1/DCAF1 E3 ubiquitin ligase complex. However, the mechanism by which SIRT7 inhibits the E3 ubiquitin ligase complex was not identified. Here, we demonstrate that SIRT7 binds directly to DDB1 and deacetylates DDB1 at Lys1121...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28622293/sumo-triggered-ubiquitination-of-nr4a1-controls-macrophage-cell-death
#18
Long Zhang, Feng Xie, Juan Zhang, Peter Ten Dijke, Fangfang Zhou
Nuclear receptor NR4A1 has been implicated as a key regulator in a wide range of pathophysiological responses. As an immediate early response gene, NR4A1 can be rapidly and potently induced by a variety of stimuli. Its induction is followed by its rapid degradation, but the mechanism by which NR4A1 is degraded remains poorly understood. Here we show that nuclear receptor NR4A1 is sumoylated by SUMO2/3. Upon poly-SUMO modification, NR4A1 can be targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28621812/tcdd-induces-ubch7-expression-and-synphilin-1-protein-degradation-in-the-mouse-ventral-midbrain
#19
Emmanuel González-Barbosa, Alejandro Mejía-García, Elizabeth Bautista, Frank J Gonzalez, José Segovia, Guillermo Elizondo
UbcH7 is an ubiquitin-conjugating enzyme that interacts with parkin, an E3 ligase. The UbcH7-parkin complex promotes the ubiquitination and degradation of several proteins via the 26S proteasome. Cellular accumulation of the UbcH7-parkin targets alpha-synuclein, and synphilin-1 has been associated with Parkinson disease. In mouse liver, 2,3,7,8-tetrachlorodibenzo-p-dioxin, an aryl hydrocarbon receptor ligand, induces UbcH7 expression. Therefore, the aim of the present study was to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin induces Ubch7 mRNA and UbcH7 protein expression in the mouse brain, to characterize the molecular mechanism, and the effect on synphilin-1 half-life...
June 16, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28620835/twenty-years-since-the-discovery-of-the-parkin-gene
#20
REVIEW
Nobutaka Hattori, Yoshikuni Mizuno
Nearly 20 years have passed since we identified the causative gene for a familial Parkinson's disease, parkin (now known as PARK2), in 1998. PARK2 is the most common gene responsible for young-onset Parkinson's disease. It codes for the protein Parkin RBR E3 ubiquitin-protein ligase (PARK2), which directly links to the ubiquitin-proteasome as a ubiquitin ligase. PARK2 is involved in mitophagy, which is a type of autophagy, in collaboration with PTEN-induced putative kinase 1 (PINK1). The PINK1 gene (previously known as PARK6) is also a causative gene for young-onset Parkinson's disease...
June 15, 2017: Journal of Neural Transmission
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