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https://www.readbyqxmd.com/read/29423113/cks1-expression-in-melanocytic-nevi-and-melanoma
#1
Anna A Brożyna, Andrew Aplin, Cynthia Cohen, Grant Carlson, Andrew Joseph Page, Michael Murphy, Andrzej T Slominski, J Andrew Carlson
Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29367551/the-potential-of-a-novel-class-of-epac-selective-agonists-to-combat-cardiovascular-inflammation
#2
REVIEW
Graeme Barker, Euan Parnell, Boy van Basten, Hanna Buist, David R Adams, Stephen J Yarwood
The cyclic 3',5'-adenosine monophosphate (cAMP) sensor enzyme, EPAC1, is a candidate drug target in vascular endothelial cells (VECs) due to its ability to attenuate proinflammatory cytokine signalling normally associated with cardiovascular diseases (CVDs), including atherosclerosis. This is through the EPAC1-dependent induction of the suppressor of cytokine signalling gene, SOCS3, which targets inflammatory signalling proteins for ubiquitinylation and destruction by the proteosome. Given this important role for the EPAC1/SOCS3 signalling axis, we have used high throughput screening (HTS) to identify small molecule EPAC1 regulators and have recently isolated the first known non-cyclic nucleotide (NCN) EPAC1 agonist, I942...
December 5, 2017: Journal of Cardiovascular Development and Disease
https://www.readbyqxmd.com/read/29363325/short-term-high-glucose-treatment-decreased-abundance-of-orai1-protein-through-posttranslational-mechanisms-in-rat-mesangial-cells
#3
Hui Jiang, Shubiao Zou, Sarika Chaudhari, Rong Ma
The short-term effect of high glucose (HG) treatment on store-operated Ca2+ entry in mesangial cells (MCs) is not well known. The aim of the present study was to determine whether and how HG treatment for a short period altered protein abundance of Orai1, the channel mediating store-operated Ca2+ entry in MCs. Rat and human MCs were exposed to HG (25 mM) for 2, 4, 8, and 24 hours and the abundance of Orai1 protein was significantly decreased at the time point of 8 and 16 hours. Consistently, HG treatment for 8 hours significantly reduced store-operated Ca2+ entry in rat MCs...
January 24, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29355525/negative-regulation-of-brca1-by-transforming-acidic-coiled-coil-protein-3-tacc3
#4
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Eun-Kyoung Breuer
In spite of the push to identify modifiers of BRCAness, it still remains unclear how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or epigenetic aberrations. Mounting evidence indicates that the transforming acidic coiled-coil 3 (TACC3) plays an important role in the centrosome-microtubule network during mitosis and gene expression, and that deregulation of TACC3 is associated with breast cancer. However, the molecular mechanisms by which TACC3 contributes to breast cancer development have yet to be elucidated...
January 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29345375/understanding-the-regulation-of-apobec3-expression-current-evidence-and-much-to-learn
#5
REVIEW
Daniela Angela Covino, Maria Cristina Gauzzi, Laura Fantuzzi
The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family of cytosine deaminases plays crucial roles in innate immunity through the ability of restricting viral replication by deamination and mutation of viral genomes. The antiviral function of these proteins was first discovered when research in the field of HIV infection revealed that one member of the family, namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral infectivity factor protein drives the proteosomal degradation of this enzyme, thus overriding its antiviral function...
December 15, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29313423/rho-guanosine-nucleotide-exchange-factors-are-not-such-bad-guys-after-all-in-cancera
#6
Javier Robles-Valero, L Francisco Lorenzo-Martín, Isabel Fernández-Pisonero, Xosé R Bustelo
Rho GDP/GTP exchange factors (GEFs), the enzymes that trigger the stimulation of Rho GTPases during cell signaling, are widely deemed as potential therapeutic targets owing to their protumorigenic functions. However, the sparse use of animal models has precluded a full understanding of their pathophysiological roles at the organismal level. In a recent article in Cancer Cell, we have reported that the Vav1 GEF unexpectedly acts as a tumor suppressor by mediating the noncatalytic nucleation of cytoplasmic complexes between the E3 ubiquitin ligase Cbl-b and the active Notch1 intracellular domain (ICN1)...
January 9, 2018: Small GTPases
https://www.readbyqxmd.com/read/29282318/src1-promotes-th17-differentiation-by-overriding-foxp3-suppression-to-stimulate-ror%C3%AE-t-activity-in-a-pkc-%C3%AE-dependent-manner
#7
Subha Sen, Fei Wang, Jing Zhang, Zhiheng He, Jian Ma, Yousang Gwack, Jianming Xu, Zuoming Sun
Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29260173/fucoidan-inhibits-amyloid-%C3%AE-induced-toxicity-in-transgenic-caenorhabditis-elegans-by-reducing-the-accumulation-of-amyloid-%C3%AE-and-decreasing-the-production-of-reactive-oxygen-species
#8
Xuelian Wang, Kaixuan Yi, Yan Zhao
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. As the aging population is increasing, AD is becoming one of the leading causes of disability and death among the elderly. However, currently there is no cure for this disease. Fucoidan is a complex sulfated polysaccharide mainly found in brown seaweed. Recent studies have shown that fucoidan is neuroprotective and may have potential to be used for treating and/or preventing neurodegenerative diseases such as AD. In this study, we investigated the effects and possible mechanisms of fucoidan on Abeta induced toxicity in a transgenic Caenorhabditis elegans (C...
December 20, 2017: Food & Function
https://www.readbyqxmd.com/read/29258576/tsetse-fly-glossina-pallidipes-midgut-responses-to-trypanosoma-brucei-challenge
#9
Rosemary Bateta, Jingwen Wang, Yineng Wu, Brian L Weiss, Wesley C Warren, Grace A Murilla, Serap Aksoy, Paul O Mireji
BACKGROUND: Tsetse flies (Glossina spp.) are the prominent vector of African trypanosome parasites (Trypanosoma spp.) in sub-Saharan Africa, and Glossina pallidipes is the most widely distributed species in Kenya. This species displays strong resistance to infection by parasites, which are typically eliminated in the midgut shortly after acquisition from the mammalian host. Although extensive molecular information on immunity for the related species Glossina morsitans morsitans exists, similar information is scarce for G...
December 19, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29233969/receptor-interacting-protein-140-as-a-co-repressor-of-heat-shock-factor-1-regulates-neuronal-stress-response
#10
Yu-Lung Lin, Hong-Chieh Tsai, Pei-Yao Liu, Michael Benneyworth, Li-Na Wei
Heat shock response (HSR) is a highly conserved transcriptional program that protects organisms against various stressful conditions. However, the molecular mechanisms modulating HSR, especially the suppression of HSR, is poorly understood. Here, we found that RIP140, a wide-spectrum cofactor of nuclear hormone receptors, acts as a co-repressor of heat shock factor 1 (HSF1) to suppress HSR in healthy neurons. When neurons are stressed such as by heat shock or sodium arsenite (As), cells engage specific proteosome-mediated degradation to reduce RIP140 level, thereby relieving the suppression and activating HSR...
December 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29157081/regulation-of-becn1-mediated-autophagy-by-hspb6-insights-from-a-human-hspb6s10f-mutant
#11
Guan-Sheng Liu, Hongyan Zhu, Wen-Feng Cai, Xiaohong Wang, Min Jiang, Kobina Essandoh, Elizabeth Vafiadaki, Kobra Haghighi, Chi Keung Lam, George Gardner, George Adly, Persoulla Nicolaou, Despina Sanoudou, Qiangrong Liang, Jack Rubinstein, Guo-Chang Fan, Evangelia G Kranias
HSPB6/Hsp20 (heat shock protein family B [small] member 6) has emerged as a novel cardioprotector against stress-induced injury. We identified a human mutant of HSPB6 (HSPB6S10F) exclusively present in dilated cardiomyopathy (DCM) patients. Cardiac expression of this mutant in mouse hearts resulted in remodeling and dysfunction, which progressed to heart failure and early death. These detrimental effects were associated with reduced interaction of mutant HSPB6S10F with BECN1/Beclin 1, leading to BECN1 ubiquitination and its proteosomal degradation...
November 20, 2017: Autophagy
https://www.readbyqxmd.com/read/29058646/vaccinia-virus-protein-a49-activates-wnt-signalling-by-targetting-the-e3-ligase-%C3%AE-trcp
#12
Carlos Maluquer de Motes, Geoffrey L Smith
Vaccinia virus (VACV) encodes multiple proteins inhibiting the NF-κB signalling pathway. One of these, A49, targets the E3 ubiquitin ligase β-TrCP, which is responsible for the ubiquitylation and consequential proteosomal degradation of IκBα and the release of the NF-κB heterodimer. β-TrCP is a pleiotropic enzyme ubiquitylating multiple cellular substrates, including the transcriptional activator β-catenin. Here we demonstrate that A49 can activate the Wnt signalling pathway, a critical pathway that is involved in cell cycle and cell differentiation, and is controlled by β-catenin...
October 17, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/29033641/do-low-serum-uch-l1-and-tdp-43-levels-indicate-disturbed-ubiquitin-proteosome-system-in-autism-spectrum-disorder
#13
İhsan Çetin, İhsan Tezdiğ, Mahmut Cem Tarakçioğlu, Muhammed Tayyib Kadak, Ömer Faruk Demirel, Ömer Faruk Özer, Fırat Erdoğan, Burak Doğangün
INTRODUCTION: The mechanism of ubiquitination-related abnormalities causing neural development problems is still unclear. We examined the association between autism and serum transactive response DNA-binding protein-43 (TDP-43) and ubiquitin c-terminal hydrolase-L1 (UCH-L1) levels, both of which are members of the ubiquitin-proteosome system. METHODS: We measured serum levels of TDP-43 and UCH-L1 in 24 children with autism and 24 healthy children. Childhood Autism Rating Scale (CARS) was used to assess symptom severity at admission...
September 2017: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/29021293/ppar%C3%AE-ligand-induced-annexin-a1-expression-determines-chemotherapy-response-via-deubiquitination-of-death-domain-kinase-rip-in-triple-negative-breast-cancers
#14
Luxi Chen, Yi Yuan, Shreya Kar, Madhu M Kanchi, Suruchi Arora, Ji E Kim, Pei F Koh, Einas Yousef, Ramar P Samy, Muthu K Shanmugam, Tuan Z Tan, Sung W Shin, Frank Arfuso, Han M Shen, Henry Yang, Boon C Goh, Joo I Park, Louis Gaboury, Peter E Lobie, Gautam Sethi, Lina H K Lim, Alan P Kumar
Metastatic breast cancer is still incurable so far; new specifically targeted and more effective therapies for triple-negative breast cancer (TNBC) are required in the clinic. In this study, our clinical data have established that basal and claudin-low subtypes of breast cancer (TNBC types) express significantly higher levels of Annexin A1 (ANXA1) with poor survival outcomes. Using human cancer cell lines that model the TNBC subtype, we observed a strong positive correlation between expression of ANXA1 and PPARγ...
August 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28981589/notch-activation-by-shootin1-opposing-activities-on-2-ubiquitin-ligases
#15
Tamar Sapir, Talia Levy, Noga Kozer, Irina Shin, Vanessa Zamor, Rebecca Haffner-Krausz, Jane C McGlade, Orly Reiner
The evolutionarily conserved Notch pathway plays an important role in regulation of stem cell renewal and cell fate determination in numerous organs, and as such is a key pathway in normal health and disease processes. Canonical Notch signaling is usually activated by cell contact where transmembrane ligands such as Delta-like and Jagged bind to Notch receptors. Notch activation results in the translocation of the cleaved Notch intracellular domain (NICD) into the nucleus and subsequent activation of transcription...
July 13, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28955980/crk-ii-silencing-down-regulates-igf-ir-and-inhibits-migration-and-invasion-of-prostate-cancer-cells
#16
Pooja Dhupkar, Huang Zhao, Kalpana Mujoo, Zhiqiang An, Ningyan Zhang
Crk (C10 regulator of kinase) adaptor proteins are highly expressed in many types of human cancers and often contribute to aggressive cancer phenotypes. Crk II, a member of CRK family, has been reported to regulate cell migration and metastasis in breast cancer cells. However, its role in other cancer types has not been reported. In this study, we investigated the molecular function of Crk II in prostate cancer (PCa) cells (CWR-22rv1) in vitro and using a mouse tumor model. Results showed that Crk II knockdown by shRNA-mediated silencing (Crk II-shRNA) in the PCa cells significantly inhibited both cancer cell migration and invasion in cell culture study...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28947489/the-plastid-and-mitochondrial-peptidase-network-in-arabidopsis-thaliana-a-foundation-for-testing-genetic-interactions-and-functions-in-organellar-proteostasis
#17
Kristina Majsec, Nazmul H Bhuiyan, Qi Sun, Sunita Kumari, Vivek Kumar, Doreen Ware, Klaas Jan van Wijk
Plant plastids and mitochondria have dynamic proteomes. Protein homeostasis in these organelles is maintained by a proteostasis network containing protein chaperones, peptidases and their substrate recognition factors. However, many peptidases, as well as their functional connections and substrates, are poorly characterized. This review provides a systematic insight into the organellar peptidase network in Arabidopsis. We present a compendium of known and putative Arabidopsis peptidases and inhibitors, and compare the distribution of plastid and mitochondrial peptidases to the total peptidase complement...
September 25, 2017: Plant Cell
https://www.readbyqxmd.com/read/28943839/cellular-chaperones-as-therapeutic-targets-in-als-to-restore-protein-homeostasis-and-improve-cellular-function
#18
REVIEW
Bernadett Kalmar, Linda Greensmith
Heat shock proteins (Hsps) are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28943305/targeting-the-cancer-epigenome-synergistic-therapy-with-bromodomain-inhibitors
#19
REVIEW
Mahalakshmi Ramadoss, Vijayalakshmi Mahadevan
Epigenetic and genomic alterations regulate the transcriptional landscape of cells during cancer onset and progression. Recent clinical studies targeting the epigenetic 'readers' (bromodomains) for cancer therapy have established the effectiveness of bromodomain (BRD) extraterminal (BET) inhibitors in treating several types of cancer. In this review, we discuss key mechanisms of BET inhibition and synergistic combinations of BET inhibitors with histone deacetylase inhibitors (HDACi), histone methyltransferase inhibitors (HMTi), DNA methyltransferase inhibitors (DNMTi), kinase, B-cell lymphoma 2 (Bcl-2) and proteosome inhibitors, and immunomodulatory drugs for cancer therapy...
September 22, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28939210/toward-a-blood-borne-biomarker-of-chronic-hypoxemia-red-cell-distribution-width-and-respiratory-disease
#20
Joseph W Yčas
Hypoxemia (systemic oxygen desaturation) marks the presence, risk, and progression of many diseases. Episodic or nocturnal hypoxemia can be challenging to detect and quantify. A sensitive, specific, and convenient marker of recent oxygen desaturation represents an unmet medical need. Observations of acclimatization to high altitude in humans and animals reveals several proteosomic, ventilatory, and hematological responses to low oxygen tension. Of these, increased red cell distribution width (RDW) appears to have the longest persistence...
2017: Advances in Clinical Chemistry
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