Browsing by author "Guettler, Sebastian"
Now showing items 1-15 of 15
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ADP-ribosyltransferases, an update on function and nomenclature.
Lüscher, B; Ahel, I; Altmeyer, M; Ashworth, A; Bai, P; et al. (WILEY, 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 (CELL PRESS, 2016-10-04)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; et al. (BMJ PUBLISHING GROUP, 2019-03-21)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 ... -
Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase.
Pollock, K; Liu, M; Zaleska, M; Meniconi, M; Pfuhl, M; et al. (NATURE PUBLISHING GROUP, 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; et al. (NATURE PUBLISHING GROUP, 2018-05-01)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; et al. (CELL PRESS, 2019-06-26)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 (Springer New York, 2017-01-01)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; et al. (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-06-01)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 ... -
Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.
Ranes, M; Zaleska, M; Sakalas, S; Knight, R; Guettler, S (CELL PRESS, 2021-08-19)The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, ... -
Regulation of Protein Interactions by Mps One Binder (MOB1) Phosphorylation.
Xiong, S; Couzens, AL; Kean, MJ; Mao, DY; Guettler, S; et al. (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-06-01)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 (WILEY, 2017-12-01)UNLABELLED: 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 ... -
Solution NMR assignment of the ARC4 domain of human tankyrase 2.
Zaleska, M; Pollock, K; Collins, I; Guettler, S; Pfuhl, M (SPRINGER, 2019-04-15)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; et al. (CELL PRESS, 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 of tankyrase activation by polymerization.
Pillay, N; Mariotti, L; Zaleska, M; Inian, O; Jessop, M; et al. (NATURE PORTFOLIO, 2022-12-01)The poly-ADP-ribosyltransferase tankyrase (TNKS, TNKS2) controls a wide range of disease-relevant cellular processes, including WNT-β-catenin signalling, telomere length maintenance, Hippo signalling, DNA damage repair and ... -
Tankyrase Requires SAM Domain-Dependent Polymerization to Support Wnt-β-Catenin Signaling.
Mariotti, L; Templeton, CM; Ranes, M; Paracuellos, P; Cronin, N; et al. (CELL PRESS, 2016-08-04)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 ...