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https://www.readbyqxmd.com/read/28743182/crosstalk-and-interplay-between-the-ubiquitin-proteasome-system-and-autophagy
#1
Chang Hoon Ji, Yong Tae Kwon
Proteolysis in eukaryotic cells is mainly mediated by the ubiquitin (Ub)-proteasome system (UPS) and the autophagylysosome system (hereafter autophagy). The UPS is a selective proteolytic system in which substrates are recognized and tagged with ubiquitin for processive degradation by the proteasome. Autophagy is a bulk degradative system that uses lysosomal hydrolases to degrade proteins as well as various other cellular constituents. Since the inception of their discoveries, the UPS and autophagy were thought to be independent of each other in components, action mechanisms, and substrate selectivity...
July 24, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28743001/gcl-and-cul3-control-the-switch-between-cell-lineages-by-mediating-localized-degradation-of-an-rtk
#2
Juhee Pae, Ryan M Cinalli, Antonio Marzio, Michele Pagano, Ruth Lehmann
The separation of germline from somatic lineages is fundamental to reproduction and species preservation. Here, we show that Drosophila Germ cell-less (GCL) is a critical component in this process by acting as a switch that turns off a somatic lineage pathway. GCL, a conserved BTB (Broad-complex, Tramtrack, and Bric-a-brac) protein, is a substrate-specific adaptor for Cullin3-RING ubiquitin ligase complex (CRL3(GCL)). We show that CRL3(GCL) promotes PGC fate by mediating degradation of Torso, a receptor tyrosine kinase (RTK) and major determinant of somatic cell fate...
July 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28742940/functional-analysis-of-the-pepper-protein-phosphatase-caaipp1-and-its-interacting-partner-caairf1-modulation-of-aba-signaling-and-the-drought-stress-response
#3
Woonhee Baek, Chae Woo Lim, Sung Chul Lee
Plant adaptive responses to abiotic stress are coordinated by restriction of plant growth and development. The plant hormone abscisic acid (ABA) is the key regulator of the response to abiotic stress, and its sensitivity determines abiotic stress tolerance levels. We previously showed that the E3 ubiquitin ligase CaAIRF1 functions as a positive regulator of ABA and drought stress via modulation of transcription and stability of the type 2C protein phosphatase CaADIP1. Here, we report the identification and functional analysis of a novel type 2C phosphatase, CaAIPP1 (Capsicum annuum CaAIRF1 Interacting Protein Phosphatase 1)...
July 25, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28742939/disparate-peroxisome-related-defects-in-arabidopsis-pex6-and-pex26-mutants-link-peroxisomal-retrotranslocation-and-oil-body-utilization
#4
Kim L Gonzalez, Wendell A Fleming, Yun-Ting Kao, Zachary J Wright, Savina V Venkova, Meredith J Ventura, Bonnie Bartel
Catabolism of fatty acids stored in oil bodies is essential for Arabidopsis seed germination and seedling development. This fatty acid breakdown occurs in peroxisomes, organelles that sequester oxidative reactions. Import of peroxisomal enzymes is facilitated by peroxins including PEX5, a receptor that delivers cargo proteins from the cytosol to the peroxisomal matrix. After cargo delivery, a complex of the PEX1 and PEX6 ATPases and the PEX26 tail-anchored membrane protein removes ubiquitinated PEX5 from the peroxisomal membrane...
July 25, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28742189/novel-endogenous-negative-modulators-of-platelet-function-as-potential-anti-thrombotic-targets
#5
Y-J Li, H-X Zhu, D Zhang, H-C Li, P Ma, L-Y Huang
Platelets are megakaryocyte-derived nuclear-free fragments that participate in cardiovascular diseases including acute myocardial infarction, ischemic stroke, hypertension, and atherosclerosis. At the endothelium damage site, platelets interact with sub-endothelial matrix proteins such as glycoprotein VI/Fc receptor γ-chain (GPVI/FcRγ), G protein-coupled receptor/phospholipase Cγ(β) (GPCR/PLCγ(β)), Rho/RhoK and integrin. The activation of these signaling pathways triggers intracellular calcium increase and causes platelet adhesion, aggregation, granule release and finally thrombus formation...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28740555/atg9b-deficiency-suppresses-autophagy-and-potentiates-endoplasmic-reticulum-stress-associated-hepatocyte-apoptosis-in-hepatocarcinogenesis
#6
Ning Wang, Hor-Yue Tan, Sha Li, Yibin Feng
The aim of this study was to investigate the mechanism underlying autophagy deficiency during hepatic carcinogenesis. For this purpose, we used choline-deficient, amino acid-defined (CDAA) hepatocarcinogenesis model in mice. miRNA microarrays combined with computational target predictions and GO analysis were used to identify molecular processes involved in carcinogenesis. PCR profiler array was employed to detect the dysregulated autophagy-related genes during carcinogenesis. We observed induction of hepatic tumours with increased inflammation, DNA damage, and cell death...
2017: Theranostics
https://www.readbyqxmd.com/read/28739485/hsp90-is-necessary-for-the-ack1-dependent-phosphorylation-of-stat1-and-stat3
#7
Nisintha Mahendrarajah, Marina E Borisova, Sigrid Reichardt, Maren Godmann, Andreas Sellmer, Siavosh Mahboobi, Andrea Haitel, Katharina Schmid, Lukas Kenner, Thorsten Heinzel, Petra Beli, Oliver H Krämer
Signal transducers and activators of transcription (STATs) are latent, cytoplasmic transcription factors. Janus kinases (JAKs) and activated CDC42-associated kinase-1 (ACK1/TNK2) catalyse the phosphorylation of STAT1 and the expression of its target genes. Here we demonstrate that catalytically active ACK1 promotes the phosphorylation and nuclear accumulation of STAT1 in transformed kidney cells. These processes are associated with STAT1-dependent gene expression and an interaction between endogenous STAT1 and ACK1...
July 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28739166/characterizing-activation-mechanisms-and-binding-preferences-of-ruthenium-metallo-prodrugs-by-a-competitive-binding-assay
#8
Christian Artner, Hannah U Holtkamp, Christian G Hartinger, Samuel M Meier-Menches
The activation mechanisms and reactivity of ruthenium metallo-prodrug lead structures were investigated in detail using capillary zone electrophoresis mass spectrometry (CZE-MS) in a time-dependent manner and by exposing to a protein/oligonucleotide mixture. The competitive assays were performed with sodium trans-[RuCl4(HInd)2] where Hind=indazole (NKP-1339), [(η(6)-p-cymene)RuCl2(pta)], where pta=1,3,5-triaza-7-phosphaadamantane (RAPTA-C) and [(η(6)-biphenyl)RuCl(1,2-ethylenediamine)]PF6 (RM175). Molecular and quantitative information on binding preferences was obtained by coupling CZE to electrospray ionization MS (ESI-MS) and inductively coupled plasma MS (ICP-MS), respectively...
July 16, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28738086/an-essential-ebv-latent-antigen-3c-binds-bcl6-for-targeted-degradation-and-cell-proliferation
#9
Yonggang Pei, Shuvomoy Banerjee, Hem Chandra Jha, Zhiguo Sun, Erle S Robertson
The latent EBV nuclear antigen 3C (EBNA3C) is required for transformation of primary human B lymphocytes. Most mature B-cell malignancies originate from malignant transformation of germinal center (GC) B-cells. The GC reaction appears to have a role in malignant transformation, in which a major player of the GC reaction is Bcl6, a key regulator of this process. We now demonstrate that EBNA3C contributes to B-cell transformation by targeted degradation of Bcl6. We show that EBNA3C can physically associate with Bcl6...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28737584/update-on-new-muscle-glycogenosis
#10
Pascal Laforêt, Edoardo Malfatti, John Vissing
PURPOSE OF REVIEW: The field of muscle glycogenoses has progressed in recent years by the identification of new disorders, and by reaching a better understanding of pathophysiology of the disorders and the physiology of glycogen metabolism. RECENT FINDINGS: In this review, we describe the clinical and pathological features of the three most recently described muscle glycogenoses caused by recessive mutations in GYG1, RBCK1 and PGM1. The three involved enzymes play different roles in glycogen metabolism...
July 21, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28737508/targeting-nek2-attenuates-glioblastoma-growth-and-radioresistance-by-destabilizing-histone-methyltransferase-ezh2
#11
Jia Wang, Peng Cheng, Marat S Pavlyukov, Hai Yu, Zhuo Zhang, Sung-Hak Kim, Mutsuko Minata, Ahmed Mohyeldin, Wanfu Xie, Dongquan Chen, Violaine Goidts, Brendan Frett, Wenhao Hu, Hongyu Li, Yong Jae Shin, Yeri Lee, Do-Hyun Nam, Harley I Kornblum, Maode Wang, Ichiro Nakano
Accumulating evidence suggests that glioma stem cells (GSCs) are important therapeutic targets in glioblastoma (GBM). In this study, we identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in GSCs. NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures (glioma spheres), and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28737031/ubiquitin-chain-enrichment-middle-down-mass-spectrometry-ubichem-ms-reveals-cell-cycle-dependent-formation-of-lys11-lys48-branched-ubiquitin-chains
#12
Ambar S J B Rana, Ying Ge, Eric R Strieter
The dynamics of cellular signaling events are tightly regulated by a diverse set of ubiquitin chains. Recent work has suggested that branched ubiquitin chains composed of Lys11 and Lys48 isopeptide linkages play a critical role in regulating cell cycle progression. Yet, endogenous Lys11/Lys48 branched chains could not be detected. By combining a Lys11 linkage specific antibody with high-resolution middle-down mass spectrometry (an approach termed UbiChEM-MS) we sought to identify endogenous Lys11/Lys48 branched ubiquitin chains in cells...
July 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28736574/elucidating-the-role-of-highly-homologous-nicotiana-benthamiana-ubiquitin-e2-gene-family-members-in-plant-immunity-through-an-improved-virus-induced-gene-silencing-approach
#13
Bangjun Zhou, Lirong Zeng
BACKGROUND: Virus-induced gene silencing (VIGS) has been used in many plant species as an attractive post transcriptional gene silencing (PTGS) method for studying gene function either individually or at large-scale in a high-throughput manner. However, the specificity and efficiency for knocking down members of a highly homologous gene family have remained to date a significant challenge in VIGS due to silencing of off-targets. RESULTS: Here we present an improved method for the selection and evaluation of gene fragments used for VIGS to specifically and efficiently knock down members of a highly homologous gene family...
2017: Plant Methods
https://www.readbyqxmd.com/read/28736168/light-dependent-degradation-of-pif3-by-scf-ebf1-2-promotes-a-photomorphogenic-response-in-arabidopsis
#14
Jie Dong, Weimin Ni, Renbo Yu, Xing Wang Deng, Haodong Chen, Ning Wei
Plant seedlings emerging from darkness into the light environment undergo photomorphogenesis, which enables autotrophic growth with optimized morphology and physiology. During this transition, plants must rapidly remove photomorphogenic repressors accumulated in the dark. Among them is PHYTOCHROME-INTERACTING FACTOR 3 (PIF3), a key transcription factor promoting hypocotyl growth. Here we report that, in response to light activation of phytochrome photoreceptors, EIN3-BINDING F BOX PROTEINs (EBFs) 1 and 2 mediate PIF3 protein degradation in a manner dependent on light-induced phosphorylation of PIF3...
July 18, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28735865/rps27a-enhances-ebv-encoded-lmp1-mediated-proliferation-and-invasion-by-stabilizing-of-lmp1
#15
Seung-Woo Hong, Seung-Mi Kim, Dong-Hoon Jin, Yeong Seok Kim, Dae Young Hur
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is an oncoviral protein that plays a pivotal role in EBV-induced oncogenic transformation. The function of LMP1 in EBV-induced oncogenesis has been well studied. However, the molecular mechanisms underlying LMP1 protein stability remain poorly understood. In this study, we found that ribosomal protein s27a (RPS27a) regulates LMP1 stability by a tandem affinity purification analysis. RPS27a interacts directly with LMP1 in vitro and in vivo. Furthermore, overexpression of RPS27a increases the half-life of LMP1 in 293T cells, whereas downregulation of RPS27a using lentiviral shRNA technology accelerates the decrease in LMP1 protein level in EBV-transformed B cells...
July 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28734869/p2x-receptors-up-regulate-the-cell-surface-expression-of-the-neuronal-glycine-transporter-glyt2
#16
Lucía Villarejo-López, Esperanza Jiménez, David Bartolomé-Martín, Francisco Zafra, Pablo Lapunzina, Carmen Aragón, Beatriz López-Corcuera
Glycinergic inhibitory neurons of the spinal dorsal horn exert critical control over the conduction of nociceptive signals to higher brain areas. The neuronal glycine transporter 2 (GlyT2) is involved in the recycling of synaptic glycine from the inhibitory synaptic cleft and its activity modulates intra and extracellular glycine concentrations. In this report we show that the stimulation of P2X purinergic receptors with βγ-methylene adenosine 5'-triphosphate induces the up-regulation of GlyT2 transport activity by increasing total and plasma membrane expression and reducing transporter ubiquitination...
July 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28734548/ubiquitin-like-modifications-in-the-dna-damage-response
#17
REVIEW
Zhifeng Wang, Wei-Guo Zhu, Xingzhi Xu
Genomic DNA is damaged at an extremely high frequency by both endogenous and environmental factors. An improper response to DNA damage can lead to genome instability, accelerate the aging process and ultimately cause various human diseases, including cancers and neurodegenerative disorders. The mechanisms that underlie the cellular DNA damage response (DDR) are complex and are regulated at many levels, including at the level of post-translational modification (PTM). Since the discovery of ubiquitin in 1975 and ubiquitylation as a form of PTM in the early 1980s, a number of ubiquitin-like modifiers (UBLs) have been identified, including small ubiquitin-like modifiers (SUMOs), neural precursor cell expressed, developmentally down-regulated 8 (NEDD8), interferon-stimulated gene 15 (ISG15), human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10), ubiquitin-fold modifier 1 (UFRM1), URM1 ubiquitin-related modifier-1 (URM1), autophagy-related protein 12 (ATG12), autophagy-related protein 8 (ATG8), fan ubiquitin-like protein 1 (FUB1) and histone mono-ubiquitylation 1 (HUB1)...
July 11, 2017: Mutation Research
https://www.readbyqxmd.com/read/28734243/caveolin-1-related-autophagy-initiated-by-aldosterone-induced-oxidation-promotes-liver-sinusoidal-endothelial-cells-defenestration
#18
Xiaoying Luo, Dan Wang, Xuan Luo, Xintao Zhu, Guozhen Wang, Zuowei Ning, Yang Li, Xiaoxin Ma, Renqiang Yang, Siyi Jin, Yun Huang, Ying Meng, Xu Li
Aldosterone, with pro-oxidation and pro-autophagy capabilities, plays a key role in liver fibrosis. However, the mechanisms underlying aldosterone-promoted liver sinusoidal endothelial cells (LSECs) defenestration remain unknown. Caveolin 1 (Cav1) displays close links with autophagy and fenestration. Hence, we aim to investigate the role of Cav1-related autophagy in LSECs defenestration. We found the increase of aldosterone/MR (mineralocorticoid receptor) level, oxidation, autophagy, and defenestration in LSECs in the human fibrotic liver, BDL or hyperaldosteronism models; while antagonizing aldosterone or inhibiting autophagy relieved LSECs defenestration in BDL-induced fibrosis or hyperaldosteronism models...
July 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28733899/6-ohda-induces-oxidation-of-f-box-protein-fbw7%C3%AE-by-chaperone-mediated-autophagy-in-parkinson-s-model
#19
Xiufeng Wang, Heng Zhai, Fang Wang
Parkinson's disease (PD) is the most common movement disorder disease, and its pathological feature is the degenerative loss of dopaminergic neurons in the substantia nigra compacta (SNc). In this study, we investigated whether distinct stress conditions target F-box protein Fbw7β via converging mechanisms. Our results showed that the 6-hyroxydopamine (6-OHDA), which causes PD in animals' models, led to decreased stability of Fbw7β in DA neuronal SN4741 cells. Further experiments suggested that oxidized Fbw7β bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity...
July 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28733455/e3-ubiquitin-ligase-nedd4-induces-endocytosis-and-lysosomal-sorting-of-connexin43-to-promote-loss-of-gap-junctions
#20
Max Z Totland, Christian H Bergsland, Tone A Fykerud, Lars M Knudsen, Nikoline L Rasmussen, Peter W Eide, Zeremariam Yohannes, Vigdis Sørensen, Andreas Brech, Ragnhild A Lothe, Edward Leithe
Intercellular communication via gap junctions has an important role in controlling cell growth and in maintaining tissue homeostasis. Connexin43 is the most abundantly expressed gap junction channel protein in humans and acts as a tumor suppressor in multiple tissue types. Connexin43 is often dysregulated at the post-translational level during cancer development, resulting in loss of gap junctions. However, the molecular basis underlying the aberrant regulation of connexin43 in cancer cells has remained elusive...
July 21, 2017: Journal of Cell Science
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