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https://www.readbyqxmd.com/read/28727686/fbxw7-regulates-disc1-stability-via-the-ubiquitin-proteosome-system
#1
K Yalla, C Elliott, J P Day, J Findlay, S Barratt, Z A Hughes, L Wilson, E Whiteley, M Popiolek, Y Li, J Dunlop, R Killick, D R Adams, N J Brandon, M D Houslay, B Hao, G S Baillie
Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28708669/the-role-of-hypothalamic-inflammation-the-hypothalamic-pituitary-adrenal-axis-and-serotonin-in-the-cancer-anorexia-cachexia-syndrome
#2
Klaske van Norren, Jvalini T Dwarkasing, Renger F Witkamp
PURPOSE OF REVIEW: In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. RECENT FINDINGS: The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients...
July 13, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28698388/delayed-cryptochrome-degradation-asymmetrically-alters-the-daily-rhythm-in-suprachiasmatic-clock-neuron-excitability
#3
Sven Wegner, Mino D C Belle, Alun T L Hughes, Casey O Diekman, Hugh D Piggins
Suprachiasmatic nuclei (SCN) neurons contain an intracellular molecular circadian clock and the Cryptochromes (CRY1/2), key transcriptional repressors of this molecular apparatus, are subject to post-translational modification through ubiquitination and targeting for proteosomal degradation by the ubiquitin E3 ligase complex. Loss-of-function point mutations in a component of this ligase complex, Fbxl3, delay CRY1/2 degradation, reduce circadian rhythm strength, and lengthen the circadian period by ∼2.5h...
July 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28691782/a-novel-microduplication-of-arid1b-clinical-genetic-and-proteomic-findings
#4
Catarina M Seabra, Nicholas Szoko, Serkan Erdin, Ashok Ragavendran, Alexei Stortchevoi, Patrícia Maciel, Kathleen Lundberg, Daniela Schlatzer, Janice Smith, Michael E Talkowski, James F Gusella, Marvin R Natowicz
Genetic alterations of ARID1B have been recently recognized as one of the most common mendelian causes of intellectual disability and are associated with both syndromic and non-syndromic phenotypes. The ARID1B protein, a subunit of the chromatin remodeling complex SWI/SNF-A, is involved in the regulation of transcription and multiple downstream cellular processes. We report here the clinical, genetic, and proteomic phenotypes of an individual with a unique apparent de novo mutation of ARID1B due to an intragenic duplication...
July 10, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28660894/proteostasis-in-cardiac-health-and-disease
#5
REVIEW
Robert H Henning, Bianca J J M Brundel
The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing...
June 29, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28659470/hepatitis-c-virus-ns5a-targets-the-nucleosome-assembly-protein-nap1l1-to-control-the-innate-cellular-response
#6
Recep Emrah Çevik, Mia Cesarec, Ana Da Silva Filipe, Danilo Licastro, John McLauchlan, Alessandro Marcello
Hepatitis C virus (HCV) is a single-stranded positive-sense RNA hepatotropic virus. Despite cellular defenses, HCV is able to replicate in hepatocytes and to establish a chronic infection that could lead to severe complications and hepatocellular carcinoma. An important player in subverting the host response to HCV infection is the viral non-structural protein NS5A that, in addition to its role in replication and assembly, targets several pathways involved in the cellular response to viral infection. Several unbiased screens identified the nucleosome-assembly protein 1-like 1 (NAP1L1) as an interaction partner of HCV NS5A...
June 28, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28652134/effects-of-thermal-stress-on-the-expression-of-glucocorticoid-receptor-complex-linked-genes-in-senegalese-sole-solea-senegalensis-acute-and-adaptive-stress-responses
#7
Vanessa Benítez-Dorta, María J Caballero, Mónica B Betancor, Manuel Manchado, Lluis Tort, Silvia Torrecillas, María J Zamorano, Marisol Izquierdo, Daniel Montero
The present study examined the short and mid-term effects of a rise in temperature from 18°C to 24°C on the expression of genes related to the stress response regulation in juveniles of Senegalese sole, Solea senegalensis. The animals were exposed to a temperature increase of 6°C, after 1month of acclimation at 18°C. After this process, samples of different tissues were collected from a total of 96 fish at four sampling points: 1h, 24h, 3days and 1week. The transcript levels of a set of genes involved in the stress response such as glucocorticoid receptors 1 and 2, corticotrophin-releasing factor, corticotrophin-releasing factor binding proteins, proopiomelanocortin A and B, and cellular stress defense (heat shock protein 70, 90AA and 90AB) were quantified at these sampling points...
June 23, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28631426/hsp90%C3%AE-regulates-atm-and-nbn-functions-in-sensing-and-repair-of-dna-double-strand-breaks
#8
Rosa Pennisi, Antonio Antoccia, Stefano Leone, Paolo Ascenzi, Alessandra di Masi
The molecular chaperone heat shock protein 90 (Hsp90α) regulates cells proteostasis and mitigates the harmful effects of endogenous and exogenous stressors on the proteome. Indeed, the inhibition of Hsp90α ATPase activity affects the cellular response to ionizing radiation (IR). Although the interplay between Hsp90α and several DNA damage response (DDR) proteins has been reported, its role in the DDR is still unclear. Here, we show that ATM and NBN, but not 53BP1, RAD50, and MRE11, are Hsp90α clients as the Hsp90α inhibitor 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) induces ATM and NBN polyubiquitination and proteosomal degradation in normal fibroblasts and lymphoblastoid cells lines...
June 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28604743/shortage-of-dntps-underlies-altered-replication-dynamics-and-dna-breakage-in-the-absence-of-the-apc-c-cofactor-cdh1
#9
J Garzón, R Rodríguez, Z Kong, A Chabes, S Rodríguez-Acebes, J Méndez, S Moreno, I García-Higuera
The APC/C-Cdh1 ubiquitin-ligase complex targets cell cycle regulators for proteosomal degradation and helps prevent tumor development and accumulation of chromosomal aberrations. Replication stress has been proposed to be the main driver of genomic instability in the absence of Cdh1, but the real contribution of APC/C-Cdh1 to efficient replication, especially in normal cells, remains unclear. Here we show that, in primary MEFs, acute depletion or permanent ablation of Cdh1 slowed down replication fork movement and increased origin activity...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28603485/multifaceted-mechanisms-of-wy-14643-to-stabilize-the-blood-brain-barrier-in-a-model-of-traumatic-brain-injury
#10
Winfried Neuhaus, Tobias Krämer, Anja Neuhoff, Christina Gölz, Serge C Thal, Carola Y Förster
The blood-brain barrier (BBB) is damaged during ischemic insults such as traumatic brain injury or stroke. This contributes to vasogenic edema formation and deteriorate disease outcomes. Enormous efforts are pursued to understand underlying mechanisms of ischemic insults and develop novel therapeutic strategies. In the present study the effects of PPARα agonist WY-14643 were investigated to prevent BBB breakdown and reduce edema formation. WY-14643 inhibited barrier damage in a mouse BBB in vitro model of traumatic brain injury based on oxygen/glucose deprivation in a concentration dependent manner...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28596494/role-of-a-kinase-anchor-protein-akap4-in-growth-and-survival-of-ovarian-cancer-cells
#11
Vikash Kumar, Nirmala Jagadish, Anil Suri
Ovarian cancer represents one of the most common malignancies among women with very high mortality rate worldwide. A-kinase anchor protein 4 (AKAP4), a unique cancer testis (CT) antigen has been shown to be associated with various malignant properties of cancer cells. However, its involvement in various molecular pathways in ovarian cancer remains unknown. In present investigation, employing gene silencing approach, we examined the role of AKAP4 in cell cycle, apoptosis and epithelial-mesenchymal transition (EMT)...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28572574/survive-or-thrive-tradeoff-strategy-for-cellular-senescence
#12
REVIEW
Sang Chul Park
Aging-dependent cellular behaviors toward extrinsic stress are characterized by the confined localization of certain molecules to either nuclear or perinuclear regions. Although most growth factors can activate downstream signaling in aging cells, they do not in fact have any impact on the cells because the signals cannot reach their genetic targets in the nucleus. For the same reason, varying apoptotic stress factors cannot stimulate the apoptotic pathway in senescent cells. Thus, the operation of a functional nuclear barrier in an aging-dependent manner has been investigated...
June 2, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28562636/a-systematic-review-of-the-asymmetric-inheritance-of-cellular-organelles-in-eukaryotes-a-critique-of-basic-science-validity-and-imprecision
#13
Anne Collins, Janine Ross, Shona H Lang
We performed a systematic review to identify all original publications describing the asymmetric inheritance of cellular organelles in normal animal eukaryotic cells and to critique the validity and imprecision of the evidence. Searches were performed in Embase, MEDLINE and Pubmed up to November 2015. Screening of titles, abstracts and full papers was performed by two independent reviewers. Data extraction and validity were performed by one reviewer and checked by a second reviewer. Study quality was assessed using the SYRCLE risk of bias tool, for animal studies and by developing validity tools for the experimental model, organelle markers and imprecision...
2017: PloS One
https://www.readbyqxmd.com/read/28559853/proteogenomics-reveals-enriched-ribosome-assembly-and-protein-translation-in-pectoralis-major-of-high-feed-efficiency-pedigree-broiler-males
#14
Walter G Bottje, Kentu Lassiter, Alissa Piekarski-Welsher, Sami Dridi, Antonio Reverter, Nicholas J Hudson, Byung-Whi Kong
Background: In production animal agriculture, the cost of feed represents 60-70% of the total cost of raising an animal to market weight. Thus, development of viable biomarkers for feed efficiency (FE, g gain/g feed) to assist in genetic selection of breeding stock remains an important goal in commercial breeding programs. Methods: Global gene (cDNA microarray, RNAseq) and protein expression (shotgun proteomics) analyses have been conducted on breast muscle samples obtained from pedigree broiler males (PedM) exhibiting high and low FE phenotypes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#15
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28475871/aging-triggers-cytoplasmic-depletion-and-nuclear-translocation-of-the-e3-ligase-mahogunin-a%C3%A2-function-for-ubiquitin-in-neuronal-survival
#16
Stefano Benvegnù, María Inés Mateo, Ernest Palomer, Jerónimo Jurado-Arjona, Carlos G Dotti
A decline in proteasome function is causally connected to neuronal aging and aging-associated neuropathologies. By using hippocampal neurons in culture and in vivo, we show that aging triggers a reduction and a cytoplasm-to-nucleus redistribution of the E3 ubiquitin ligase mahogunin (MGRN1). Proteasome impairment induces MGRN1 monoubiquitination, the key post-translational modification for its nuclear entry. One potential mechanism for MGRN1 monoubiquitination is via progressive deubiquitination at the proteasome of polyubiquitinated MGRN1...
May 4, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28465486/overexpression-of-sphk2-contributes-to-atra-resistance-in-colon-cancer-through-rapid-degradation-of-cytoplasmic-rxr%C3%AE-by-k48-k63-linked-polyubiquitination
#17
Wen-Na Shi, Shu-Xiang Cui, Zhi-Yu Song, Shu-Qing Wang, Shi-Yue Sun, Xin-Feng Yu, Ye Li, Yu-Hang Zhang, Zu-Hua Gao, Xian-Jun Qu
The resistance mechanisms that limit the efficacy of retinoid therapy in cancer are poorly understood. Sphingosine kinase 2 (SphK2) is a highly conserved enzyme that is mainly located in the nucleus and endoplasmic reticulum. Unlike well-studied sphingosine kinase 1 (SphK1) located in the cytosol, little has yet understood the functions of SphK2. Here we show that SphK2 overexpression contributes to the resistance of all-trans retinoic acid (ATRA) therapy in colon cancer through rapid degradation of cytoplasmic retinoid X receptor α (RXRα) by lysine 48 (K48)- and lysine 63 (K63)-based polyubiquitination...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28441528/phosphorylation-of-neurog3-links-endocrine-differentiation-to-the-cell-cycle-in-pancreatic-progenitors
#18
Nicole A J Krentz, Dennis van Hoof, Zhongmei Li, Akie Watanabe, Mei Tang, Cuilan Nian, Michael S German, Francis C Lynn
During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28400504/cardiopulmonary-phenotype-associated-with-human-phd2-mutation
#19
Nick P Talbot, Thomas G Smith, George M Balanos, Keith L Dorrington, Patrick H Maxwell, Peter A Robbins
Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28380042/genetic-and-pharmacological-inhibition-of-ttk-impairs-pancreatic-cancer-cell-line-growth-by-inducing-lethal-chromosomal-instability
#20
Jeran K Stratford, Feng Yan, Rebecca A Hill, Michael B Major, Lee M Graves, Channing J Der, Jen Jen Yeh
Pancreatic ductal adenocarcinoma, which accounts for the majority of pancreatic cancers, is a lethal disease with few therapeutic options. Genomic profiling of pancreatic ductal adenocarcinoma has identified a complex and heterogeneous landscape. Understanding the molecular characteristics of pancreatic ductal adenocarcinoma will facilitate the identification of potential therapeutic strategies. We analyzed the gene expression profiles of primary tumors from patients compared to normal pancreas and identified high co-overexpression of core components of the spindle assembly checkpoint, including the protein kinase TTK (also known as MPS-1)...
2017: PloS One
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