Show simple item record

dc.contributor.authorRowling, Pamela JE
dc.contributor.authorMurton, Ben L
dc.contributor.authorDu, Zhen
dc.contributor.authorItzhaki, Laura S
dc.date.accessioned2022-06-29T19:43:36Z
dc.date.available2022-06-29T19:43:36Z
dc.date.issued2022
dc.date.submitted2022-03-15
dc.identifier.issn2296-889X
dc.identifier.other896493
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338457
dc.description.abstractThe Wnt signalling pathway plays key roles in cell proliferation, differentiation and fate decisions in embryonic development and maintenance of adult tissues, and the twelve Armadillo (ARM) repeat-containing protein β-catenin acts as the signal transducer in this pathway. Here we investigate the interaction between β-catenin's ARM repeat domain and the intrinsically disordered protein adenomatous polyposis coli (APC). APC is a giant multivalent scaffold that brings together the different components of the so-called "β-catenin destruction complex", which drives β-catenin degradation via the ubiquitin-proteasome pathway. Mutations and truncations in APC, resulting in loss of APC function and hence elevated β-catenin levels and upregulation of Wnt signalling, are associated with numerous cancers including colorectal carcinomas. APC has a long intrinsically disordered region (IDR) that contains a series of 15-residue and 20-residue binding regions for β-catenin. Here we explore the multivalent nature of the interaction of β-catenin with the highest affinity APC repeat, both at equilibrium and under kinetic conditions. We use a combination of single-site substitutions, deletions and insertions to dissect the mechanism of molecular recognition and the roles of the three β-catenin-binding subdomains of APC.
dc.languageen
dc.publisherFrontiers Media SA
dc.subjectMolecular Biosciences
dc.subjectbeta-catenin (β-catenin)
dc.subjectadenomatous polyposis coli (APC)
dc.subjectintrinsically disordered protein
dc.subjectprotein-protein interaction (PPI)
dc.subjectmultivalency
dc.subjectfuzzy binding
dc.subjectarmadillo repeat
dc.titleMultivalent Interaction of Beta-Catenin With its Intrinsically Disordered Binding Partner Adenomatous Polyposis Coli.
dc.typeArticle
dc.date.updated2022-06-29T19:43:36Z
prism.publicationNameFront Mol Biosci
prism.volume9
dc.identifier.doi10.17863/CAM.85870
dcterms.dateAccepted2022-05-02
rioxxterms.versionofrecord10.3389/fmolb.2022.896493
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.identifier.eissn2296-889X
cam.issuedOnline2022-06-08


Files in this item

Thumbnail
Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record