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dc.contributor.authorMariotti, Len_US
dc.contributor.authorPollock, Ken_US
dc.contributor.authorGuettler, Sen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-11-27T15:33:48Z
dc.date.accessioned2018-11-29T09:17:59Z
dc.date.issued2017-12en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28910490en_US
dc.identifier.citationBr J Pharmacol, 2017, 174 (24), pp. 4611 - 4636en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2961
dc.identifier.eissn1476-5381en_US
dc.identifier.doi10.1111/bph.14038en_US
dc.description.abstractThe 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 through the concerted interactions of concentration-limited pathway components and a wide range of post-translational modifications, including phosphorylation, ubiquitylation, sumoylation, poly(ADP-ribosyl)ation (PARylation) and acetylation. Regulation of Wnt/β-catenin signalling by PARylation was discovered relatively recently. The PARP tankyrase PARylates AXIN1/2, an essential central scaffolding protein in the β-catenin destruction complex, and targets it for degradation, thereby fine-tuning the responsiveness of cells to the Wnt signal. The past few years have not only seen much progress in our understanding of the molecular mechanisms by which PARylation controls the pathway but also witnessed the successful development of tankyrase inhibitors as tool compounds and promising agents for the therapy of Wnt-dependent dysfunctions, including colorectal cancer. Recent work has hinted at more complex roles of tankyrase in Wnt/β-catenin signalling as well as challenges and opportunities in the development of tankyrase inhibitors. Here we review some of the latest advances in our understanding of tankyrase function in the pathway and efforts to modulate tankyrase activity to re-tune Wnt/β-catenin signalling in colorectal cancer cells. LINKED ARTICLES: This article is part of a themed section on WNT Signalling: Mechanisms and Therapeutic Opportunities. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.24/issuetoc.en_US
dc.format.extent4611 - 4636en_US
dc.languageengen_US
dc.language.isoengen_US
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/2958
dc.relation.replacesinternal/2958
dc.relation.replacesinternal/806
dc.relation.replaceshttps://repository.icr.ac.uk/handle/internal/806
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectAnimalsen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectColorectal Neoplasmsen_US
dc.subjectEnzyme Inhibitorsen_US
dc.subjectHumansen_US
dc.subjectPoly ADP Ribosylationen_US
dc.subjectTankyrasesen_US
dc.subjectWnt Signaling Pathwayen_US
dc.titleRegulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-08-07en_US
rioxxterms.versionofrecord10.1111/bph.14038en_US
rioxxterms.licenseref.startdate2017-12en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBr J Pharmacolen_US
pubs.declined2017-09-01T12:06:04.215+0100
pubs.issue24en_US
pubs.merge-frominternal/806
pubs.merge-fromhttps://repository.icr.ac.uk/handle/internal/806
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicinal Chemistry 2
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Structural Biology of Cell Signalling
pubs.publication-statusPublisheden_US
pubs.volume174en_US
pubs.embargo.termsNot knownen_US
icr.researchteamMedicinal Chemistry 2en_US
icr.researchteamStructural Biology of Cell Signallingen_US
dc.contributor.icrauthorGuettler, Sebastianen_US
dc.contributor.icrauthorMariotti, Lauraen_US
dc.contributor.icrauthorPollock, Katieen_US


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