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https://www.readbyqxmd.com/read/29680823/prodomain-of-furin-promotes-phospholipid-transfer-protein-proteasomal-degradation-in-hepatocytes
#1
Yang Yu, Xia Lei, Hui Jiang, Zhiqiang Li, John W M Creemers, Ming Zhang, Shucun Qin, Weijun Jin, Xian-Cheng Jiang
BACKGROUND: Phospholipid transfer protein (PLTP) is one of the major modulators of lipoprotein metabolism and atherosclerosis development; however, little is known about the regulation of PLTP. The effect of hepatic prodomain of furin (profurin) expression on PLTP processing and function is investigated. METHODS AND RESULTS: We used adenovirus expressing profurin in mouse liver to evaluate PLTP activity, mass, and plasma lipid levels. We coexpressed PLTP and profurin in human hepatoma cell line cells and studied their interaction...
April 21, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29679638/inhibition-of-immunoproteasome-promotes-angiogenesis-via-enhancing-hypoxia-inducible-factor-1%C3%AE-abundance-in-rats-following-focal-cerebral-ischaemia
#2
Xingyong Chen, Xu Zhang, Ting Chen, Xiulong Jiang, Xiaosong Wang, Huixin Lei, Yinzhou Wang
Angiogenesis after ischemic stroke contributes to the restoration of blood supply in the ischemic zone. Strategies to improve angiogenesis may facilitate the function recovery after stroke. Growing evidence shows that proteasome inhibitors enhance angioneurogenesis and induces a long-term neuroprotection after cerebral ischemia in rodents' models. We have previously reported that inhibition of the immunoproteasome subunit low molecular mass peptide 2 (LMP2) offers a strong neuroprotection in ischemic stroke rats...
April 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29679567/hdac-mediated-deacetylation-of-klf5-associates-with-its-proteasomal-degradation
#3
Ran Tao, Baotong Zhang, Yixiang Li, Jamie L King, Ruoyu Tian, Siyuan Xia, Cara Rae Schiavon, Jin-Tang Dong
Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145. While confirming the functions of HDAC1/2 in KLF5 deacetylation and the promotion of cell proliferation, we found that the knockdown of HDAC1/2 upregulated KLF5 protein but not KLF5 mRNA, and the increase in KLF5 protein level by silencing HDAC1/2 was at least in part due to decreased proteasomal degradation...
April 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29679004/the-linc01138-drives-malignancies-via-activating-arginine-methyltransferase-5-in-hepatocellular-carcinoma
#4
Zhe Li, Jiwei Zhang, Xinyang Liu, Shengli Li, Qifeng Wang, Di Chen, Zhixiang Hu, Tao Yu, Jie Ding, Jinjun Li, Ming Yao, Jia Fan, Shenglin Huang, Qiang Gao, Yingjun Zhao, Xianghuo He
Recurrent chromosomal aberrations have led to the discovery of oncogenes or tumour suppressors involved in carcinogenesis. Here we characterized an oncogenic long intergenic non-coding RNA in the frequent DNA-gain regions in hepatocellular carcinoma (HCC), LINC01138 (long intergenic non-coding RNA located on 1q21.2). The LINC01138 locus is frequently amplified in HCC; the LINC01138 transcript is stabilized by insulin like growth factor-2 mRNA-binding proteins 1/3 (IGF2BP1/IGF2BP3) and is associated with the malignant features and poor outcomes of HCC patients...
April 20, 2018: Nature Communications
https://www.readbyqxmd.com/read/29678583/identifying-the-sumo1-modification-of-fam122a-leading-to-the-degradation-of-pp2a-c%C3%AE-by-ubiquitin-proteasome-system
#5
Fangzhi Fan, Junxing Zhao, Yali Liu, Hongfang Zhao, Lietao Weng, Qingqing Li, Guoqiang Chen, Ying Xu
FAM122A is a highly conserved protein in mammals. Here, we identify that FAM122A can be sumoylated at lysine 89, which can be de-conjugated by SENP1. Furthermore, the sumoylation of FAM122A reduces the PP2A-Cα protein level together with the reduced phosphatase activity of PP2A, which suppresses cell proliferation. Collectively, our results suggest that the sumoylation of FAM122A may have a significant role in cellular function.
April 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29678181/a20-deubiquitinase-controls-pgc-1%C3%AE-expression-in-the-adipose-tissue
#6
Bruna Bombassaro, Leticia M Ignacio-Souza, Carla E Nunez, Daniela S Razolli, Rafael M Pedro, Andressa Coope, Eliana P Araujo, Elinton A Chaim, Licio A Velloso
BACKGROUND: Peroxisome proliferator-activated receptor γ coactivator- 1alpha (PGC-1α) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is highly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1α degradation. METHODS: Here we evaluated the interaction of PGC-1α with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase...
April 20, 2018: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29678103/ouantitative-proteomic-analysis-of-cellular-responses-to-a-designed-amino-acid-feed-in-a-monoclonal-antibody-producing-chinese-hamster-ovary-cell-line
#7
Fatemeh Torkashvand, Fereidoun Mahboudi, Manouchehr Vossoughi, Elnaz Fatemi, Seyed Masoud Moosavi Basri, Amir Heydari, Behrouz Vaziri
Background: Chinese hamster ovary (CHO) cell line is considered as the most common cell line in the biopharmaceutical industry because of its capability in performing efficient post-translational modifications and producing the recombinant proteins, which are similar to natural human proteins. The optimization of the upstream process via different feed strategies has a great impact on the target molecule expression and yield. Methods: To determine and understand the molecular events beneath the feed effects on the CHO cell, a label-free quantitative proteomic analysis was applied...
April 21, 2018: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/29677518/retraction-notice-to-atp-hydrolysis-dependent-disassembly-of-the-26s-proteasome-is-part-of-the-catalytic-cycle
#8
Shalon E Babbitt, Alexi Kiss, Andrew E Deffenbaugh, Yie-Hwa Chang, Eric Bailly, Hediye Erdjument-Bromage, Paul Tempst, Tione Buranda, Larry A Sklar, Jennifer Baumler, Edward Gogol, Dorota Skowyra
No abstract text is available yet for this article.
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29676528/e3-ubiquitin-ligase-rnf123-targets-lamin-b1-and-lamin-binding-proteins
#9
Richa Khanna, Vidhya Krishnamoorthy, Veena K Parnaik
Lamins are key nuclear proteins which are important for maintaining nuclear structure and function. Mutations in lamins cause a spectrum of genetic diseases termed as laminopathies. RING finger containing E3 ubiquitin ligase, RNF123 is transcriptionally upregulated in cells expressing rod-domain lamin A mutations. However, the functional relevance of RNF123 in laminopathic cells is not clear. Using a mass spectrometry based approach, we identified lamins and lamin-binding proteins retinoblastoma protein (pRb), lamina-associated polypeptide 2α (LAP2α) and emerin as RNF123-interacting proteins...
April 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29676460/resistance-to-proteasome-inhibitors-and-other-targeted-therapies-in-myeloma
#10
REVIEW
Craig T Wallington-Beddoe, Magdalena Sobieraj-Teague, Bryone J Kuss, Stuart M Pitson
The number of novel therapies for the treatment of myeloma is rapidly increasing, as are the clinical trials evaluating them in combination with other novel and established therapies. Proteasome inhibitors, immunomodulatory agents and monoclonal antibodies are the most well known and studied classes of novel agents targeting myeloma, with histone deacetylase inhibitors, nuclear export inhibitors and several other approaches also being actively investigated. However, in parallel with the development and clinical use of these novel myeloma therapies is the emergence of novel mechanisms of resistance, many of which remain elusive, particularly for more recently developed agents...
April 20, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29674748/itraq-based-quantitative-proteomic-analysis-of-embryonic-developmental-stages-in-amur-sturgeon-acipenser-schrenckii
#11
Shubo Jin, Dajiang Sun, Dan Song, Nianmin Wang, Hongtuo Fu, Feng Ji, Ying Zhang
The Amur sturgeon, Acipenser schrenckii, is an important aquaculture species in China with annual production of about 150 thousand tons in 2015. In this study, we investigated the regulatory proteins and pathways affecting embryonic development of Amur sturgeon, by analyzing of the differential proteomes among four embryonic developmental stages using isobaric tags for relative and absolute quantitation (iTRAQ), combined with the analysis of effects of microelements and antioxidants on embryonic development...
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29674291/molecular-modeling-on-porphyrin-derivatives-as-%C3%AE-5-subunit-inhibitor-of-20s-proteasome
#12
Muhammad Arba, Andry Nur-Hidayat, Ruslin, Muhammad Yusuf, Sumarlin, Rukman Hertadi, Setyanto Tri Wahyudi, Slamet Ibrahim Surantaadmaja, Daryono H Tjahjono
The ubiquitin-proteasome system plays an important role in protein quality control. Currently, inhibition of the proteasome has been validated as a promising approach in anticancer therapy. The 20S core particle of the proteasome harbors β5 subunit which is a crucial active site in proteolysis. Targeting proteasome β5 subunit which is responsible for the chymotrypsin-like activity of small molecules has been regarded as an important way for achieving therapeutics target. In the present study, a series of porphyrin derivatives bearing either pyridine or pyrazole rings as meso-substituents were designed and evaluated as an inhibitor for the β5 subunit of the proteasome by employing molecular docking and dynamics simulations...
April 16, 2018: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/29673970/the-role-of-compartmentalized-signaling-pathways-in-the-control-of-mitochondrial-activities-in-cancer-cells
#13
REVIEW
Laura Rinaldi, Rossella Delle Donne, Domenica Borzacchiello, Luigi Insabato, Antonio Feliciello
Mitochondria are the powerhouse organelles present in all eukaryotic cells. They play a fundamental role in cell respiration, survival and metabolism. Stimulation of G-protein coupled receptors (GPCRs) by dedicated ligands and consequent activation of the cAMP·PKA pathway finely coupleenergy production and metabolism to cell growth and survival. Compartmentalization of PKA signaling at mitochondria by A-Kinase Anchor Proteins (AKAPs) ensures efficient transduction of signals generated at the cell membrane to the organelles, controlling important aspects of mitochondrial biology...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29672276/blocking-p62-sqstm1-dependent-smn-degradation-ameliorates-spinal-muscular-atrophy-disease-phenotypes
#14
Natalia Rodriguez-Muela, Andrey Parkhitko, Tobias Grass, Rebecca M Gibbs, Erika M Norabuena, Norbert Perrimon, Rajat Singh, Lee L Rubin
Spinal muscular atrophy (SMA), a degenerative motor neuron (MN) disease caused by loss of functional SMN protein due to SMN1 gene mutations, is a leading cause of infant mortality. Increasing SMN levels ameliorates the disease phenotype and is unanimously accepted as a therapeutic approach for SMA patients. The ubiquitin/proteasome system is known to regulate SMN protein levels; however whether autophagy controls SMN levels remains poorly explored. Here we show that SMN protein is degraded by autophagy. Pharmacological and genetic inhibition of autophagy increase SMN levels, while induction of autophagy decreases SMN...
April 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29670681/diaphragm-muscle-weakness-following-acute-sustained-hypoxic-stress-in-the-mouse-is-prevented-by-pretreatment-with-n-acetyl-cysteine
#15
Andrew J O'Leary, Sarah E Drummond, Deirdre Edge, Ken D O'Halloran
Oxygen deficit (hypoxia) is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2  = 0.10) with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.). Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS) were determined...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29670521/the-prenylflavonoid-xanthohumol-reduces-alzheimer-like-changes-and-modulates-multiple-pathogenic-molecular-pathways-in-the-neuro2a-app-swe-cell-model-of-ad
#16
Xianfeng Huang, Jing Wang, Xiao Chen, Pan Liu, Shujin Wang, Fangchen Song, Zaijun Zhang, Feiqi Zhu, Xinfeng Huang, Jianjun Liu, Guoqiang Song, Peter S Spencer, Xifei Yang
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop ( Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29670089/rest-regulated-by-ra-through-mir-29a-and-the-proteasome-pathway-plays-a-crucial-role-in-rpc-proliferation-and-differentiation
#17
Yuyao Wang, Dandan Zhang, Zhimin Tang, Yi Zhang, Huiqin Gao, Ni Ni, Bingqiao Shen, Hao Sun, Ping Gu
One of the primary obstacles in the application of retinal progenitor cells (RPCs) to the treatment of retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), is their limited ability to proliferate and differentiate into specific retinal neurons. In this study, we revealed that repressor element-1-silencing transcription factor (REST), whose expression could be transcriptionally and post-transcriptionally mediated by retinoic acid (RA, one isomeride of a vitamin A derivative used as a differentiation-inducing agent in many disease treatments), plays a pivotal role in the regulation of proliferation and differentiation of RPCs...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29670085/a-trib2-p38-axis-controls-myeloid-leukaemia-cell-cycle-and-stress-response-signalling
#18
Mara Salomé, Aoife Magee, Krisha Yalla, Shahzya Chaudhury, Evgenia Sarrou, Ruaidhrí J Carmody, Karen Keeshan
Trib2 pseudokinase is involved in the etiology of a number of cancers including leukaemia, melanoma, ovarian, lung and liver cancer. Both high and low Trib2 expression levels correlate with different types of cancer. Elevated Trib2 expression has oncogenic properties in both leukaemia and lung cancer dependent on interactions with proteasome machinery proteins and degradation of transcription factors. Here, we demonstrated that Trib2 deficiency conferred a growth and survival advantage both at steady state and in stress conditions in leukaemia cells...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29669860/thermal-proteome-profiling-of-breast-cancer-cells-reveals-proteasomal-activation-by-cdk4-6-inhibitor-palbociclib
#19
Teemu P Miettinen, Julien Peltier, Anetta Härtlova, Marek Gierliński, Valerie M Jansen, Matthias Trost, Mikael Björklund
Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that is not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it...
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669812/tankyrase-modulates-insulin-sensitivity-in-skeletal-muscle-cells-by-regulating-the-stability-of-glut4-vesicle-proteins
#20
Zhiduan Su, Vinita Deshpande, David E James, Jacqueline Stöckli
Tankyrase1 and 2, members of the poly(ADP-ribose) polymerase family, have previously been shown to play a role in insulin-mediated glucose uptake in adipocytes. However, their precise mechanism of action, and their role in insulin action in other cell types, such as myocytes, remains elusive. Treatment of differentiated L6 myotubes with the small molecule tankyrase inhibitor XAV939 resulted in insulin resistance as determined by impaired insulin-stimulated glucose uptake. Proteomic analysis of XAV939-treated myotubes identified down-regulation of several glucose transporter GLUT4 storage vesicle (GSV) proteins including RAB10, VAMP8, SORT1 and GLUT4...
April 18, 2018: Journal of Biological Chemistry
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