Now showing items 32-51 of 58

    • 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)
    • Solution NMR assignment of the ARC4 domain of human tankyrase 2. 

      Zaleska, M; Pollock, K; Collins, I; Guettler, S; Pfuhl, M (2019-04)
      Tankyrases are poly(ADP-ribose)polymerases (PARPs) which recognize their substrates via their ankyrin repeat cluster (ARC) domains. The human tankyrases (TNKS/TNKS2) contain five ARCs in their extensive N-terminal region; ...
    • Structural Basis for a Reciprocal Regulation between SCF and CSN 

      Enchev, RI; Scott, DC; da Fonseca, PCA; Schreiber, A; Monda, JK; Schulman, BA; Peter, M; Morris, EP
    • Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment. 

      Xiong, S; Lorenzen, K; Couzens, AL; Templeton, CM; Rajendran, D; Mao, DYL; Juang, Y-C; Chiovitti, D; Kurinov, I; Guettler, S; Gingras, A-C; Sicheri, F (2018-08-07)
      The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase ...
    • Structural basis for translocation by AddAB helicase-nuclease and its arrest at χ sites. 

      Krajewski, WW; Fu, X; Wilkinson, M; Cronin, NB; Dillingham, MS; Wigley, DB (2014-04)
      In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence χ (Chi) and is catalysed by either an AddAB- or RecBCD-type ...
    • Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome. 

      Faull, SV; Lau, AMC; Martens, C; Ahdash, Z; Hansen, K; Yebenes, H; Schmidt, C; Beuron, F; Cronin, NB; Morris, EP; Politis, A (2019-08-23)
      Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures ...
    • Structural basis of RNA polymerase III transcription initiation. 

      Abascal-Palacios, G; Ramsay, EP; Beuron, F; Morris, E; Vannini, A (2018-01-17)
      RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene ...
    • Structural rearrangements of the RNA polymerase III machinery during tRNA transcription initiation. 

      Ramsay, EP; Vannini, A (2018-04)
      RNA polymerase III catalyses the synthesis of tRNAs in eukaryotic organisms. Through combined biochemical and structural characterisation, multiple auxiliary factors have been identified alongside RNA Polymerase III as ...
    • Structure-based drug design: aiming for a perfect fit. 

      van Montfort, RLM; Workman, P (2017-11-08)
      Knowledge of the three-dimensional structure of therapeutically relevant targets has informed drug discovery since the first protein structures were determined using X-ray crystallography in the 1950s and 1960s. In this ...