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UBiquitine

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https://www.readbyqxmd.com/read/28647906/exogenous-gdf11-induces-cardiac-and-skeletal-muscle-dysfunction-and-wasting
#1
Teresa A Zimmers, Yanling Jiang, Meijing Wang, Tiffany W Liang, Joseph E Rupert, Ernie D Au, Francesco E Marino, Marion E Couch, Leonidas G Koniaris
Growth differentiation factor 11 (GDF11), a TGF-beta superfamily member, is highly homologous to myostatin and essential for embryonic patterning and organogenesis. Reports of GDF11 effects on adult tissues are conflicting, with some describing anti-aging and pro-regenerative activities on the heart and skeletal muscle while others opposite or no effects. Herein, we sought to determine the in vivo cardiac and skeletal muscle effects of excess GDF11. Mice were injected with GDF11 secreting cells, an identical model to that used to initially identify the in vivo effects of myostatin...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28647685/irtks-is-correlated-with-progression-and-survival-time-of-patients-with-gastric-cancer
#2
Li-Yu Huang, Xuefei Wang, Xiao-Fang Cui, He Li, Junjie Zhao, Chong-Chao Wu, Lingqiang Min, Zhicheng Zhou, Lixin Wan, Yu-Ping Wang, Chao Zhang, Wei-Qiang Gao, Yihong Sun, Ze-Guang Han
BACKGROUND AND OBJECTIVES: IRTKS functions as a novel regulator of tumour suppressor p53; however, the role of IRTKS in pathogenesis of gastric cancer is unclear. DESIGN: We used immunohistochemistry to detect IRTKS levels in 527 human gastric cancer specimens. We generated both IRTKS-deficient and p53-deficient mice to observe survival time of these mice and to isolate mouse embryonic fibroblasts (MEFs) for evaluating in vivo tumorigenicity. Co-immunoprecipitation was used to study the interaction among p53, MDM2 and IRTKS, as well as the ubiquitination of p53...
June 24, 2017: Gut
https://www.readbyqxmd.com/read/28647409/a-residue-specific-insight-into-the-arkadia-e3-ubiquitin-ligase-activity-and-conformational-plasticity
#3
Maria Birkou, Christos T Chasapis, Konstantinos D Marousis, Ariadni K Loutsidou, Detlef Bentrop, Moreno Lelli, Torsten Herrmann, Jonathon M Carthy, Vasso Episkopou, Georgios A Spyroulias
Arkadia (Rnf111) is an E3 Ubiquitin ligase that plays a central role in the amplification of TGF-β signaling responses by targeting for degradation the negative regulators of the pathway, Smad6 and Smad7 and the nuclear co-repressors Ski and Skil (SnoN). Arkadia's function in vivo depends on the RING-H2 interaction with the E2 enzyme UbcH5b in order to ligate ubiquitin chains on its substrates. A conserved tryptophan (W972) in the C-terminal α-helix is widely accepted as essential for E2 recruitment and interaction and thus also for E3 enzymatic activity...
June 21, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28647349/inhibitor-of-apoptosis-proteins-iaps-limit-ripk1-mediated-skin-inflammation
#4
H Anderton, J A Rickard, G A Varigos, N Lalaoui, J Silke
Inhibitor of Apoptosis Proteins (IAPs) are critical regulators of cell death and survival pathways. Mice lacking cellular IAP (cIAP) 1 and either cIAP2 or X-linked IAP (XIAP) die in utero, and myeloid lineage-specific deletion of all IAPs causes sterile inflammation, but their role in the skin is unknown. We generated epidermal-specific IAPs deficient mice and found that combined genetic deletion of cIAP1 in keratinocytes and ubiquitous cIAP2 deletion (cIap1(EKO/EKO).cIap2(-/-)) caused profound skin inflammation and keratinocyte death, lethal by post-partum day 10...
June 21, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646551/prospero-related-homeobox-1-drives-angiogenesis-of-hepatocellular-carcinoma-through-selectively-activating-il-8-expression
#5
Yanfeng Liu, Yonglong Zhang, Shenghao Wang, Qiong-Zhu Dong, Zhongliang Shen, Wei Wang, Shuai Tao, Chenjian Gu, Jing Liu, Youhua Xie, Lun-Xiu Qin
Angiogenesis has been proven to play an important role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying HCC angiogenesis is not well understood. In this study, Prospero-related homeobox 1 (PROX1) was identified as a novel pro-angiogenic factor in HCC cell lines and tissues. A strong positive correlation was found between the levels of PROX1 and microvessel density in HCC tissues. Knockdown of PROX1 expression in HCC cells significantly inhibited the in vitro capillary tube formation by human vascular endothelial cells and in vivo angiogenesis of HCC, while overexpression of PROX1 in HCC cells induced the opposite effects...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28646424/proteasome-properties-of-hemocytes-differ-between-the-whiteleg-shrimp-penaeus-vannamei-and-the-brown-shrimp-crangon-crangon-crustacea-decapoda
#6
Sandra Götze, Reinhard Saborowski, Oliviert Martínez-Cruz, Adriana Muhlia-Almazán, Arturo Sánchez-Paz
Crustaceans are intensively farmed in aquaculture facilities where they are vulnerable to parasites, bacteria, or viruses, often severely compromising the rearing success. The ubiquitin-proteasome system (UPS) is crucial for the maintenance of cellular integrity. Analogous to higher vertebrates, the UPS of crustaceans may also play an important role in stress resistance and pathogen defense. We studied the general properties of the proteasome system in the hemocytes of the whiteleg shrimp, Penaeus vannamei, and the European brown shrimp Crangon crangon...
June 23, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28646136/recurrent-background-mutations-in-whi2-impair-proteostasis-and-degradation-of-misfolded-cytosolic-proteins-in-saccharomyces-cerevisiae
#7
Sophie A Comyn, Stéphane Flibotte, Thibault Mayor
Proteostasis promotes viability at both the cellular and organism levels by maintaining a functional proteome. This requires an intricate protein quality control (PQC) network that mediates protein folding by molecular chaperones and removes terminally misfolded proteins via the ubiquitin proteasome system and autophagy. How changes within the PQC network can perturb proteostasis and shift the balance between protein folding and proteolysis remain poorly understood. However, given that proteostasis is altered in a number of conditions such as cancer and ageing, it is critical that we identify the factors that mediate PQC and understand the interplay between members of the proteostatic network...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28645578/the-electrophilic-character-of-quinones-is-essential-for-the-suppression-of-bach1
#8
Chuanyang Su, Zixuan Liu, Yawen Wang, Yuxin Wang, Erqun Song, Yang Song
The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is the most important cellular defense mechanisms against oxidative attack. BTB and CNC homology-1 (Bach1), like Kelch-like ECH-associated protein 1 (Keap1), is one of a negative regulator of Nrf2 that control antioxidant response elements (ARE)-dependent gene expressions. In the current study, we found that quinones show greater capacity than hydroquinones in nuclear Bach1 export, as well as ubiquitin-dependent Bach1 degradation in our experimental time frame...
June 20, 2017: Toxicology
https://www.readbyqxmd.com/read/28643728/regulation-of-various-dna-repair-pathways-by-e3-ubiquitin-ligases
#9
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/28640887/epidermal-growth-factor-promotes-cyclin-g2-degradation-via-calpain-mediated-proteolysis-in-gynaecological-cancer-cells
#10
Stefanie Bernaudo, Shahin Khazai, Eilyad Honarparvar, Alina Kopteva, Chun Peng
Cyclin G2 (CCNG2) is an atypical cyclin that functions to inhibit cell cycle progression and is often dysregulated in human cancers. We have previously shown that cyclin G2 is highly unstable and can be degraded through the ubiquitin/proteasome pathway. Furthermore, cyclin G2 contains a PEST domain, which has been suggested to act as a signal for degradation by multiple proteases. In this study, we determined if calpains, a family of calcium-dependent proteases, are also involved in cyclin G2 degradation. The addition of calpain inhibitors or silencing of calpain expression by siRNAs strongly enhanced cyclin G2 levels...
2017: PloS One
https://www.readbyqxmd.com/read/28640445/ubiquitin-ligases-and-posttranslational-regulation-of-energy-in-the-heart-the-hand-that-feeds
#11
David I Brown, Traci L Parry, Monte S Willis
Heart failure (HF) is a costly and deadly syndrome characterized by the reduced capacity of the heart to adequately provide systemic blood flow. Mounting evidence implicates pathological changes in cardiac energy metabolism as a contributing factor in the development of HF. While the main source of fuel in the healthy heart is the oxidation of fatty acids, in the failing heart the less energy efficient glucose and glycogen metabolism are upregulated. The ubiquitin proteasome system plays a key role in regulating metabolism via protein-degradation/regulation of autophagy and regulating metabolism-related transcription and cell signaling processes...
June 18, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28640357/rna-sequencing-of-esophageal-adenocarcinomas-identifies-novel-fusion-transcripts-including-npc1-melk-arising-from-a-complex-chromosomal-rearrangement
#12
Zhixiong Wang, Yulan Cheng, John M Abraham, Rong Yan, Xi Liu, Wei Chen, Sariat Ibrahim, Gary P Schroth, Xiquan Ke, Yulong He, Stephen J Meltzer
BACKGROUND: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). METHODS: To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28640253/a-role-for-tspo-in-mitochondrial-ca-2-homeostasis-and-redox-stress-signaling
#13
Jemma Gatliff, Daniel A East, Aarti Singh, Maria Soledad Alvarez, Michele Frison, Ivana Matic, Caterina Ferraina, Natalie Sampson, Federico Turkheimer, Michelangelo Campanella
The 18 kDa translocator protein TSPO localizes on the outer mitochondrial membrane (OMM). Systematically overexpressed at sites of neuroinflammation it is adopted as a biomarker of brain conditions. TSPO inhibits the autophagic removal of mitochondria by limiting PARK2-mediated mitochondrial ubiquitination via a peri-organelle accumulation of reactive oxygen species (ROS). Here we describe that TSPO deregulates mitochondrial Ca(2+) signaling leading to a parallel increase in the cytosolic Ca(2+) pools that activate the Ca(2+)-dependent NADPH oxidase (NOX) thereby increasing ROS...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28639727/switching-futile-para-quinone-to-efficient-ros-generator-ubiquitin-specific-protease-2-inhibition-electrocatalysis-and-quantification
#14
Ashraf Brik, Pushparathinam Gopinath, Atif Mahammed, Tal Eilon-Shaffer, Mickal Nawatha, Shimrit Ohayon, Doron Shabat, Zeev Gross
Understanding the correlation between structural features of small molecule drugs to its mode of action is a fascinating topic and crucial for the drug discovery process. However, in many cases the exact parameters that dictate the mode of action is still lacking. Following a large screening for USP2 inhibition identified effective para-quinone based inhibitor with unclear mode of action. For gaining a deep knowledge on its mechanism of inhibition, a set of para-quinones was prepared and studied for USP2 inhibition, electrocatalysis and ROS quantification...
June 22, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28639716/expression-of-the-autoantigen-trim33-tif1%C3%AE-in-skin-and-muscle-of-patients-with-dermatomyositis-is-upregulated-together-with-markers-of-cellular-stress
#15
B Scholtissek, S Ferring-Schmitt, J Maier, J Wenzel
Dermatomyositis (DM) is an autoimmune disorder associated with a dysregulation of immune homeostasis of both the innate and adaptive immune system. Earlier data suggested that these two arms of the immune system interconnect in DM. In the current study, we analysed the association of autoantigen expression [adaptive system components: Mi2, transcriptional intermediary factor (TIF)1γ, small ubiquitin-like modifier 1 activating enzyme subunit (SAE)1, melanoma differentiation-associated protein (MDA)5] with markers of cellular stress (innate system components: MxA, p53) in skin and muscle (immunohistology and gene expression data, respectively)...
June 22, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28639696/modulation-of-global-sumoylation-by-kaposi-s-sarcoma-associated-herpesvirus-and-its-effects-on-viral-gene-expression
#16
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/28639322/tnf-%C3%AE-induced-nod2-and-rip2-contribute-to-the-up-regulation-of-cytokines-induced-by-mdp-in-monocytic-thp-1-cells
#17
Xiaobin Chen, Zhilin Xiao, Xiumei Xie, Xueting Liu, Manli Jiang, Chuang Yuan, Li Yang, Jinyue Hu
Nucleotide-binding oligomerization domain containing 2 (NOD2)-induced signal transduction and cytokine production is regulated by a number of factors. However, the feedback effect of the pro-inflammatory TNF-α on NOD2-induced inflammation is not fully understood. In this study, we found unexpectedly that TNF-α up-regulated NOD2 ligand MDP-induced production of the CXC chemokines, including CXCL1, 2 and 8, and the pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α, in a dose-dependent manner at both mRNA and protein levels in monocytic THP-1 cells...
June 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28638917/influence-of-sodium-nitroprusside-on-expressions-of-fbxl5-and-irp2-in-sh-sy5y-cells
#18
Jie Wei, Yong Li, Qian Jiao, Xi-Xun DU, Hong Jiang
Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease (PD). Misexpression of some iron transport and storage proteins is related to iron dyshomeostasis. Iron regulatory proteins (IRPs) including IRP1 and IRP2 are cytosolic proteins that play important roles in maintaining cellular iron homeostasis. F-box and leucine-rich repeat protein 5 (FBXL5) is involved in the regulation of iron metabolism by degrading IRP2 through the ubiquitin-proteasome system. Nitric oxide (NO) enhances the binding activity of IRP1, but its effect on IRP2 is ambiguous...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28638054/drug-repositioning-screening-for-keap1-nrf2-binding-inhibitors-using-fluorescence-correlation-spectroscopy
#19
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/28637674/oxidative-stress-destabilizes-protein-arginine-methyltransferase-4-via-glycogen-synthase-kinase-3%C3%AE-to-impede-lung-epithelial-cell-migration
#20
Xiuying Li, Yandong Lai, Jin Li, Mingyi Zou, Chunbin Zou
Oxidative stress impacts normal cellular function leading to the pathogenesis of various diseases including pulmonary illnesses. Protein arginine methyltransferase 4 (PRMT4) is critical for normal lung alveolar epithelial cell development; however, the regulation of PRMT4 within such pulmonary diseases has yet to be elucidated. Using biochemical approaches, we uncovered that peroxide (H2O2) treatment decreases PRMT4 protein stability in murine lung epithelial (MLE12) cells to impede cell migration. Protein kinase glycogen synthase kinase 3β (GSK-3β) interacts with PRMT4 and catalyzes PRMT4 T132 phosphorylation that protects PRMT4 from ubiquitin proteasomal degradation...
June 21, 2017: American Journal of Physiology. Cell Physiology
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