Now showing items 1-13 of 13

    • ADP-ribosyltransferases, an update on function and nomenclature. 

      Lüscher, B; Ahel, I; Altmeyer, M; Ashworth, A; Bai, P; Chang, P; Cohen, M; Corda, D; Dantzer, F; Daugherty, MD; Dawson, TM; Dawson, VL; Deindl, S; Fehr, AR; Feijs, KLH; Filippov, DV; Gagné, J-P; Grimaldi, G; Guettler, S; Hoch, NC; Hottiger, MO; Korn, P; Kraus, WL; Ladurner, A; Lehtiö, L; Leung, AKL; Lord, CJ; Mangerich, A; Matic, I; Matthews, J; Moldovan, G-L; Moss, J; Natoli, G; Nielsen, ML; Niepel, M; Nolte, F; Pascal, J; Paschal, BM; Pawłowski, K; Poirier, GG; Smith, S; Timinszky, G; Wang, Z-Q; Yélamos, J; Yu, X; Zaja, R; Ziegler, M (2021-07-29)
      ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- ...
    • AXIN Shapes Tankyrase ARChitecture. 

      Guettler, S (2016-10)
      The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein ...
    • CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids. 

      Gonzalez-Exposito, R; Semiannikova, M; Griffiths, B; Khan, K; Barber, LJ; Woolston, A; Spain, G; von Loga, K; Challoner, B; Patel, R; Ranes, M; Swain, A; Thomas, J; Bryant, A; Saffery, C; Fotiadis, N; Guettler, S; Mansfield, D; Melcher, A; Powles, T; Rao, S; Watkins, D; Chau, I; Matthews, N; Wallberg, F; Starling, N; Cunningham, D; Gerlinger, M (2019-04-15)
      Background The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high levels ...
    • Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase. 

      Pollock, K; Liu, M; Zaleska, M; Meniconi, M; Pfuhl, M; Collins, I; Guettler, S (2019-12-13)
      The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer. 

      Woolston, A; Khan, K; Spain, G; Barber, LJ; Griffiths, B; Gonzalez-Exposito, R; Hornsteiner, L; Punta, M; Patil, Y; Newey, A; Mansukhani, S; Davies, MN; Furness, A; Sclafani, F; Peckitt, C; Jiménez, M; Kouvelakis, K; Ranftl, R; Begum, R; Rana, I; Thomas, J; Bryant, A; Quezada, S; Wotherspoon, A; Khan, N; Fotiadis, N; Marafioti, T; Powles, T; Lise, S; Calvo, F; Guettler, S; von Loga, K; Rao, S; Watkins, D; Starling, N; Chau, I; Sadanandam, A; Cunningham, D; Gerlinger, M (2019-07)
      Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ...
    • Identifying and Validating Tankyrase Binders and Substrates: A Candidate Approach. 

      Pollock, K; Ranes, M; Collins, I; Guettler, S (2017-01)
      The poly(ADP-ribose)polymerase (PARP) enzyme tankyrase (TNKS/ARTD5, TNKS2/ARTD6) uses its ankyrin repeat clusters (ARCs) to recognize degenerate peptide motifs in a wide range of proteins, thereby recruiting such proteins ...
    • 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 ...
    • Regulation of Protein Interactions by <i>M</i>ps <i>O</i>ne <i>B</i>inder (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/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 ...
    • 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 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)
      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 ...
    • Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling. 

      Mariotti, L; Templeton, CM; Ranes, M; Paracuellos, P; Cronin, N; Beuron, F; Morris, E; Guettler, S (2016-08)
      The poly(ADP-ribose) polymerase (PARP) Tankyrase (TNKS and TNKS2) is paramount to Wnt-β-catenin signaling and a promising therapeutic target in Wnt-dependent cancers. The pool of active β-catenin is normally limited by ...