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https://www.readbyqxmd.com/read/28332498/a-genome-wide-screen-identifies-yap-wbp2-interplay-conferring-growth-advantage-on-human-epidermal-stem-cells
#1
Gernot Walko, Samuel Woodhouse, Angela Oliveira Pisco, Emanuel Rognoni, Kifayathullah Liakath-Ali, Beate M Lichtenberger, Ajay Mishra, Stephanie B Telerman, Priyalakshmi Viswanathan, Meike Logtenberg, Lisa M Renz, Giacomo Donati, Sven R Quist, Fiona M Watt
Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28330616/systematic-analysis-of-human-protein-phosphatase-interactions-and-dynamics
#2
Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, Markku Varjosalo
Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28325843/a-biochemical-framework-for-eif4e-dependent-mrna-export-and-nuclear-re-cycling-of-the-export-machinery
#3
Laurent Volpon, Biljana Culjkovic-Kraljacic, Hye Seon Sohn, Alexis Blanchett-Cohen, Michael J Osborne, Katherine L B Borden
The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ~50 nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end...
March 21, 2017: RNA
https://www.readbyqxmd.com/read/28322318/12-o-tetradecanoylphorbol-13-acetate-tpa-is-anti-tumorigenic-in-liver-cancer-cells-via-inhibiting-yap-through-amot
#4
Guoqing Zhu, Yan Chen, Xiao Zhang, Qi Wu, Yinghui Zhao, Yuxin Chen, Fenyong Sun, Yongxia Qiao, Jiayi Wang
TPA stimulates carcinogenesis in various types of cancers. However, we found that TPA inhibits transformative phenotypes in liver cancer cells via the translocation of YAP from the nucleus, where it functions as a transcriptional co-factor, to the cytoplasm. Such effects led to a separation of YAP from its dependent transcription factors. The inhibitory effects of TPA on YAP were AMOT dependent. Without AMOT, TPA was unable to alter YAP activity. Importantly, the depletion of YAP and AMOT blocked the TPA-reduced transformative phenotypes...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315703/molecular-endocrinology-of-vitamin-d-on-the-epigenome-level
#5
REVIEW
Carsten Carlberg
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28303012/tryptophan-end-tagging-for-promoted-lipopolysaccharide-interactions-and-anti-inflammatory-effects
#6
Shalini Singh, Aritreyee Datta, Artur Schmidtchen, Anirban Bhunia, Martin Malmsten
The objective of the present study is the investigation of possibilities for boosting peptide anti-inflammatory effects by tryptophan end-tagging, including identification of underlying mechanisms for this. In doing so, effects of tryptophan end-tagging of KYE21 (KYEITTIHNLFRKLTHRLFRR), a peptide derived from heparin co-factor II, on membrane and lipopolysaccharide (LPS) interactions were investigated by ellipsometry, NMR, fluorescence spectroscopy, and circular dichroism measurements. Through its N-terminal W stretch, WWWKYE21 displays higher membrane binding, liposome rupture, and bacterial killing than unmodified KYE21...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302936/cryotolerance-of-porcine-blastocysts-is-improved-by-treating-in-vitro-matured-oocytes-with-l-carnitine-prior-to-fertilization
#7
Jenna L Lowe, Louise K Bartolac, Roslyn Bathgate, Christopher G Grupen
Sufficient generation of adenosine triphosphate (ATP) by oocytes is critical for fertilization and embryo development. The objective of this study was to determine the effects of supplementing media with L-carnitine, a co-factor required for the metabolism of fatty acids, during the peri-fertilization period on embryo development and energy generation. Firstly, in vitro fertilization (IVM) porcine oocytes were co-incubated with sperm in IVF medium supplemented with 0‒24 mM L-carnitine. The blastocyst formation rate of the control group was greater than those of the L-carnitine groups (P < 0...
March 16, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28301169/conformational-dynamics-of-cyanocobalamin-and-its-conjugates-with-peptide-nucleic-acids
#8
Tomasz Pieńko, Aleksandra J Wierzba, Monika Wojciechowska, Dorota Gryko, Joanna Trylska
Vitamin B12 also called cobalamin (Cbl) is an important enzymatic co-factor taken up by mammalian and also by many bacterial cells. Peptide nucleic acid (PNA) is a synthetic DNA analogue that has the ability to bind in a complementary manner to natural nucleic acids. Provided that PNA is efficiently delivered to cells, it could act as a steric blocker of functional DNA or RNA and regulate gene expression at the level of transcription or translation. Recently, Cbl has been examined as a transporter of various molecules to cells...
March 16, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28299664/roles-of-runx-in-b-cell-immortalisation
#9
Michelle J West, Paul J Farrell
RUNX1 and RUNX3 are the main RUNX genes expressed in B lymphocytes. Both are expressed throughout B-cell development and play key roles at certain key developmental transitions. The tumour-associated Epstein-Barr virus (EBV) has potent B-cell transforming ability and manipulates RUNX3 and RUNX1 transcription through novel mechanisms to control B cell growth. In contrast to resting mature B cells where RUNX1 expression is high, in EBV-infected cells RUNX1 levels are low and RUNX3 levels are high. Downregulation of RUNX1 in these cells results from cross-regulation by RUNX3 and serves to relieve RUNX1-mediated growth repression...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299651/runx1-structure-and-function-in-blood-cell-development
#10
Constanze Bonifer, Elena Levantini, Valerie Kouskoff, Georges Lacaud
RUNX transcription factors belong to a highly conserved class of transcriptional regulators which play various roles in the development of the majority of metazoans. In this review we focus on the founding member of the family, RUNX1, and its role in the transcriptional control of blood cell development in mammals. We summarize data showing that RUNX1 functions both as activator and repressor within a chromatin environment, a feature that requires its interaction with multiple other transcription factors and co-factors...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299193/recent-advances-in-major-histocompatibility-complex-mhc-class-i-antigen-presentation-plastic-mhc-molecules-and-tapbpr-mediated-quality-control
#11
REVIEW
Andy van Hateren, Alistair Bailey, Tim Elliott
We have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity...
2017: F1000Research
https://www.readbyqxmd.com/read/28296634/constitutive-scaffolding-of-multiple-wnt-enhanceosome-components-by-legless-bcl9
#12
Laurens M van Tienen, Juliusz Mieszczanek, Marc Fiedler, Trevor J Rutherford, Mariann Bienz
Wnt/β-catenin signaling elicits context-dependent transcription switches that determine normal development and oncogenesis. These are mediated by the Wnt enhanceosome, a multiprotein complex binding to the Pygo chromatin reader and acting through TCF/LEF-responsive enhancers. Pygo renders this complex Wnt-responsive, by capturing β-catenin via the Legless/BCL9 adaptor. We used CRISPR/Cas9 genome engineering of Drosophila legless (lgs) and human BCL9 and B9L to show that the C-terminus downstream of their adaptor elements is crucial for Wnt responses...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28292191/upper-calyx-accessibility-through-a-lower-calyx-access-is-not-influenced-by-morphometric-and-clinical-factors-in-supine-percutaneous-nephrolithotomy
#13
Mario Sofer, Yazeed Barghouthy, Yuval Bar-Yosef, Ishay Mintz, Silvia Proietti, Ronit Tsemah, Amir Horkin, Haim Matzkin, Guido Giusti
OBJECTIVE: To assess whether morphometric and clinical parameters influence accessibility to the upper calyx through a lower calyx tract during supine percutaneous nephrolithotomy (SPCNL). METHODS: Data for 114 consecutive SPCNLs performed between 6/2014-3/2016 in an academic medical center were analyzed. Successful approachability was defined as rigid nephroscopic access to the upper calyx introduced through a lower calyx access as attested by direct visualization of the upper calyx papillae and position of the nephroscope on intraoperative pyelography...
March 14, 2017: Journal of Endourology
https://www.readbyqxmd.com/read/28291240/testosterone-levels-in-pre-menopausal-women-are-associated-with-nonalcoholic-fatty-liver-disease-in-midlife
#14
Monika Sarkar, Melissa Wellons, Marcelle I Cedars, Lisa VanWagner, Erica P Gunderson, Veeral Ajmera, Laura Torchen, David Siscovick, J Jeffrey Carr, James G Terry, Mary Rinella, Cora E Lewis, Norah Terrault
OBJECTIVES: Young women with hyperandrogenism have high risk of metabolic co-morbidities, including increased risk of nonalcoholic fatty liver disease (NAFLD). Whether testosterone (the predominant androgen) is associated with NAFLD independent of metabolic co-factors is unclear. Additionally, whether testosterone confers increased risk of NAFLD in women without hyperandrogenism is unknown. METHODS: Among women in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether free testosterone levels measured at Year 2 (1987-1988) were associated with prevalent NAFLD at Year 25 (2010-2011) (n=1052)...
March 14, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28285996/a-sterile-20-family-kinase-and-its-co-factor-ccm-3-regulate-contractile-ring-proteins-on-germline-intercellular-bridges
#15
Kathryn Rehain-Bell, Andrew Love, Michael E Werner, Ian MacLeod, John R Yates, Amy Shaub Maddox
Germ cells in most animals are connected by intercellular bridges, actin-based rings that form stable cytoplasmic connections between cells promoting communication and coordination [1]. Moreover, these connections are required for fertility [1, 2]. Intercellular bridges are proposed to arise from stabilization of the cytokinetic ring during incomplete cytokinesis [1]. Paradoxically, proteins that promote closure of cytokinetic rings are enriched on stably open intercellular bridges [1, 3, 4]. Given this inconsistency, the mechanism of intercellular bridge stabilization is unclear...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28265619/influence-of-ph-and-mg-ii-on-the-catalytic-core-domain-5-of-a-bacterial-group-ii-intron
#16
M Pechlaner, A Dominguez-Martin, R K O Sigel
RNA molecules fold into complex structures that allow them to perform specific functions. To compensate the relative lack of diversity of functional groups within nucleotides, metal ions work as crucial co-factors. In addition, shifted pKas are observed in RNA, enabling acid-base reactions at ambient pH. The central catalytic domain 5 (D5) hairpin of the Azotobacter vinelandii group II intron undergoes both metal ion binding and pH dependence, presumably playing an important functional role in the ribozyme's reaction...
March 21, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28263970/cytosolic-malate-dehydrogenase-activity-helps-support-glycolysis-in-actively-proliferating-cells-and-cancer
#17
E A Hanse, C Ruan, M Kachman, D Wang, X H Lowman, A Kelekar
Increased glucose consumption is a hallmark of cancer cells. The increased consumption and subsequent metabolism of glucose during proliferation creates the need for a constant supply of NAD, a co-factor in glycolysis. Regeneration of the NAD required to support enhanced glycolysis has been attributed to the terminal glycolytic enzyme, lactate dehydrogenase (LDH). However, loss of glucose carbons to biosynthetic pathways early in glycolysis reduces the carbon supply to LDH. Thus, alternative routes for NAD regeneration must exist to support the increased glycolytic rate while allowing for the diversion of glucose to generate biomass and support proliferation...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28263788/discovery-of-a-novel-oocyte-specific-kr%C3%A3-ppel-associated-box-domain-containing-zinc-finger-protein-required-for-early-embryogenesis-in-cattle
#18
Jacqelyn M Hand, Kun Zhang, Lei Wang, Prasanthi P Koganti, Kristen Mastrantoni, Sandeep K Rajput, Mohamed Ashry, George W Smith, Jianbo Yao
Zinc finger (ZNF) transcription factors interact with DNA through zinc finger motifs and play important roles in a variety of cellular functions including cell growth, proliferation, development, apoptosis, and intracellular signal transduction. One-third of ZNF proteins in metazoans contain a highly conserved N-terminal motif known as the Krüppel-associated box (KRAB) domain, which acts as a potent, DNA-binding dependent transcriptional repression module. Analysis of RNA-Seq data generated from a bovine oocyte cDNA library identified a novel transcript, which encodes a KRAB-containing ZNF transcription factor (named ZNFO)...
March 2, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28257976/the-pbx1-lupus-susceptibility-gene-regulates-cd44-expression
#19
Yuxin Niu, Mayami Sengupta, Anton A Titov, Seung-Chul Choi, Laurence Morel
PBX1-d is novel splice isoform of pre-B-cell leukemia homeobox 1 (PBX1) that lacks its DNA-binding and Hox-binding domains, and functions as a dominant negative. We have shown that PBX1-d expression in CD4(+) T cells is associated with systemic lupus erythematosus (SLE) in a mouse model as well as in human subjects. More specifically, PBX1-d expression leads to the production of autoreactive activated CD4+ T cells, a reduced frequency and function of Foxp3+ regulatory T (Treg) cells and an expansion of follicular helper T (Tfh) cells...
February 28, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28257867/cobalamin-supplementation-during-in%C3%A2-vitro-maturation-improves-developmental-competence-of-sheep-oocytes
#20
Federica Zacchini, Paola Toschi, Grazyna Ewa Ptak
Pregnancies obtained by Assisted Reproductive Technologies are at higher risk of miscarriage than those obtained naturally. Previously, we reported impaired placental vascular development of in vitro produced (IVP) sheep embryos and defective DNA methylation in the placentae of those embryos. One reason behind these observed defects may be an impaired One Carbon Metabolism (OCM) The present study was performed to test the hypothesis that Cobalamin (Vitamin B12, an important OCM co-factor) supplementation during IVM corrects DNA methylation of IVP embryos and, consequently, ameliorates placental vasculogenesis...
April 15, 2017: Theriogenology
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