Now showing items 21-40 of 52

    • Mechanism of selective recruitment of RNA polymerases II and III to snRNA gene promoters. 

      Dergai, O; Cousin, P; Gouge, J; Satia, K; Praz, V; Kuhlman, T; Lhôte, P; Vannini, A; Hernandez, N (2018-05-01)
      RNA polymerase II (Pol II) small nuclear RNA (snRNA) promoters and type 3 Pol III promoters have highly similar structures; both contain an interchangeable enhancer and "proximal sequence element" (PSE), which recruits the ...
    • MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. 

      Lampis, A; Carotenuto, P; Vlachogiannis, G; Cascione, L; Hedayat, S; Burke, R; Clarke, P; Bosma, E; Simbolo, M; Scarpa, A; Yu, S; Cole, R; Smyth, E; Mateos, JF; Begum, R; Hezelova, B; Eltahir, Z; Wotherspoon, A; Fotiadis, N; Bali, MA; Nepal, C; Khan, K; Stubbs, M; Hahne, JC; Gasparini, P; Guzzardo, V; Croce, CM; Eccles, S; Fassan, M; Cunningham, D; Andersen, JB; Workman, P; Valeri, N; Braconi, C (2018-03)
      BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ...
    • MOB1 Mediated Phospho-recognition in the Core Mammalian Hippo Pathway. 

      Couzens, AL; Xiong, S; Knight, JDR; Mao, DY; Guettler, S; Picaud, S; Kurinov, I; Filippakopoulos, P; Sicheri, F; Gingras, A-C (2017-06)
      The Hippo tumor suppressor pathway regulates organ size and tissue homoeostasis in response to diverse signaling inputs. The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate ...
    • Molecular mechanisms of Bdp1 in TFIIIB assembly and RNA polymerase III transcription initiation. 

      Gouge, J; Guthertz, N; Kramm, K; Dergai, O; Abascal-Palacios, G; Satia, K; Cousin, P; Hernandez, N; Grohmann, D; Vannini, A (2017-07-25)
      Initiation of gene transcription by RNA polymerase (Pol) III requires the activity of TFIIIB, a complex formed by Brf1 (or Brf2), TBP (TATA-binding protein), and Bdp1. TFIIIB is required for recruitment of Pol III and to ...
    • Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737). 

      Osborne, JD; Matthews, TP; McHardy, T; Proisy, N; Cheung, KM; Lainchbury, M; Brown, N; Walton, MI; Eve, PD; Boxall, KJ; Hayes, A; Henley, AT; Valenti, MR; De Haven Brandon, AK; Box, G; Jamin, Y; Robinson, SP; Westwood, IM; van Montfort, RL; Leonard, PM; Lamers, MB; Reader, JC; Aherne, GW; Raynaud, FI; Eccles, SA; Garrett, MD; Collins, I (2016-06)
      Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ...
    • Myosin and Actin Filaments in Muscle: Structures and Interactions. 

      Squire, JM; Paul, DM; Morris, EP (2017)
      In the last decade, improvements in electron microscopy and image processing have permitted significantly higher resolutions to be achieved (sometimes <1 nm) when studying isolated actin and myosin filaments. In the case ...
    • Nanostructures from Synthetic Genetic Polymers. 

      Taylor, AI; Beuron, F; Peak-Chew, SY; Morris, EP; Herdewijn, P; Holliger, P (2016-06)
      Nanoscale objects of increasing complexity can be constructed from DNA or RNA. However, the scope of potential applications could be enhanced by expanding beyond the moderate chemical diversity of natural nucleic acids. ...
    • New tricks for an old dog: Brf2-dependent RNA Polymerase III transcription in oxidative stress and cancer. 

      Gouge, J; Vannini, A (2018)
      Here, we discuss the role of Brf2, an RNA Polymerase III core transcription factor, as a master switch of the oxidative stress response. We highlight the interplay of Brf2 with the Nrf2/Keap1 pathway, as well as the role ...
    • Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. 

      Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; Khan, K; Lampis, A; Eason, K; Huntingford, I; Burke, R; Rata, M; Koh, D-M; Tunariu, N; Collins, D; Hulkki-Wilson, S; Ragulan, C; Spiteri, I; Moorcraft, SY; Chau, I; Rao, S; Watkins, D; Fotiadis, N; Bali, M; Darvish-Damavandi, M; Lote, H; Eltahir, Z; Smyth, EC; Begum, R; Clarke, PA; Hahne, JC; Dowsett, M; de Bono, J; Workman, P; Sadanandam, A; Fassan, M; Sansom, OJ; Eccles, S; Starling, N; Braconi, C; Sottoriva, A; Robinson, SP; Cunningham, D; Valeri, N (2018-02-23)
      Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
    • Privileged Structures and Polypharmacology within and between Protein Families. 

      Meyers, J; Chessum, NEA; Ali, S; Mok, NY; Wilding, B; Pasqua, AE; Rowlands, M; Tucker, MJ; Evans, LE; Rye, CS; O'Fee, L; Le Bihan, Y-V; Burke, R; Carter, M; Workman, P; Blagg, J; Brown, N; van Montfort, RLM; Jones, K; Cheeseman, MD (2018-12-13)
      Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ...
    • Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. 

      Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; Cronin, N; Hayes, A; Roberts, J; Henley, AT; Baker, R; Faisal, A; Mak, GW; Box, G; Valenti, M; De Haven Brandon, A; O'Fee, L; Saville, H; Schmitt, J; Matijssen, B; Burke, R; van Montfort, RL; Raynaud, FI; Eccles, SA; Linardopoulos, S; Blagg, J; Hoelder, S (2016-04-07)
      Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ...
    • RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases. 

      Lin, Y-H; Lucas, M; Evans, TR; Abascal-Palacios, G; Doms, AG; Beauchene, NA; Rojas, AL; Hierro, A; Machner, MP (2018-02)
      The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational ...
    • Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. 

      Gouge, J; Satia, K; Guthertz, N; Widya, M; Thompson, AJ; Cousin, P; Dergai, O; Hernandez, N; Vannini, A (2015-12)
      TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine ...
    • Regulation of Protein Interactions by Mps One Binder (MOB1) Phosphorylation. 

      Xiong, S; Couzens, AL; Kean, MJ; Mao, DY; Guettler, S; Kurinov, I; Gingras, A-C; Sicheri, F (2017-06)
      MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases ...
    • Regulation of Wnt/ß-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding 

      Mariotti, L; Pollock, K; Guettler, S (Wiley-Blackwell, 2017-09-14)
    • Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

      Mariotti, L; Pollock, K; Guettler, S (2017-12)
      The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
    • Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

      Mariotti, L; Pollock, K; Guettler, S (2017-12)
      The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
    • Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism. 

      Paul, DM; Squire, JM; Morris, EP (2017-03)
      The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca2+ using electron microscopy and reference-free single particle ...
    • REVEL: an Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. 

      Ioannidis, NM; Rothstein, JH; Pejaver, V; Middha, S; McDonnell, SK; Baheti, S; Musolf, A; Li, Q; Holzinger, E; Karyadi, D; Cannon-Albright, LA; Teerlink, CC; Stanford, JL; Isaacs, WB; Xu, J; Cooney, KA; Lange, EM; Schleutker, J; Carpten, JD; Powell, IJ; Cussenot, O; Cancel-Tassin, G; Giles, GG; MacInnis, RJ; Maier, C; Hsieh, CL; Wiklund, F; Catalona, WJ; Foulkes, WD; Mandal, D; Eeles, RA; Kote-Jarai, Z; Bustamante, CD; Schaid, DJ; Hastie, T; Ostrander, EA; Bailey-Wilson, JE; Radivojac, P; Thibodeau, SN; Whittemore, AS; Sieh, W (2016-09-21)
      The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the ...
    • RNA polymerase I, bending the rules? 

      Jochem, L; Ramsay, EP; Vannini, A (2017-09-15)