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dc.contributor.authorWigington, CPen_US
dc.contributor.authorRoy, Jen_US
dc.contributor.authorDamle, NPen_US
dc.contributor.authorYadav, VKen_US
dc.contributor.authorBlikstad, Cen_US
dc.contributor.authorResch, Een_US
dc.contributor.authorWong, CJen_US
dc.contributor.authorMackay, DRen_US
dc.contributor.authorWang, JTen_US
dc.contributor.authorKrystkowiak, Ien_US
dc.contributor.authorBradburn, DAen_US
dc.contributor.authorTsekitsidou, Een_US
dc.contributor.authorHong, SHen_US
dc.contributor.authorKaderali, MAen_US
dc.contributor.authorXu, S-Len_US
dc.contributor.authorStearns, Ten_US
dc.contributor.authorGingras, A-Cen_US
dc.contributor.authorUllman, KSen_US
dc.contributor.authorIvarsson, Yen_US
dc.contributor.authorDavey, NEen_US
dc.contributor.authorCyert, MSen_US
dc.date.accessioned2020-09-30T11:07:08Z
dc.date.issued2020-07-08en_US
dc.identifier.citationMolecular cell, 2020, 79 (2), pp. 342 - 358.e12en_US
dc.identifier.issn1097-2765en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4095
dc.identifier.eissn1097-4164en_US
dc.identifier.doi10.1016/j.molcel.2020.06.029en_US
dc.description.abstractShort linear motifs (SLiMs) drive dynamic protein-protein interactions essential for signaling, but sequence degeneracy and low binding affinities make them difficult to identify. We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/PP2B, the Ca<sup>2+</sup>-activated phosphatase that recognizes LxVP and PxIxIT motifs. In vitro proteome-wide detection of CN-binding peptides, in vivo SLiM-dependent proximity labeling, and in silico modeling of motif determinants uncovered unanticipated CN interactors, including NOTCH1, which we establish as a CN substrate. Unexpectedly, CN shows SLiM-dependent proximity to centrosomal and nuclear pore complex (NPC) proteins-structures where Ca<sup>2+</sup> signaling is largely uncharacterized. CN dephosphorylates human and yeast NPC proteins and promotes accumulation of a nuclear transport reporter, suggesting conserved NPC regulation by CN. The CN network assembled here provides a resource to investigate Ca<sup>2+</sup> and CN signaling and demonstrates synergy between experimental and computational methods, establishing a blueprint for examining SLiM-based networks.en_US
dc.formatPrint-Electronicen_US
dc.format.extent342 - 358.e12en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHela Cellsen_US
dc.subjectCentrosomeen_US
dc.subjectHumansen_US
dc.subjectSaccharomyces cerevisiaeen_US
dc.subjectPhosphoric Monoester Hydrolasesen_US
dc.subjectCalcineurinen_US
dc.subjectNuclear Pore Complex Proteinsen_US
dc.subjectSaccharomyces cerevisiae Proteinsen_US
dc.subjectProteomeen_US
dc.subjectBiotinylationen_US
dc.subjectSignal Transductionen_US
dc.subjectAmino Acid Motifsen_US
dc.subjectActive Transport, Cell Nucleusen_US
dc.subjectPhosphorylationen_US
dc.subjectComputer Simulationen_US
dc.subjectReceptor, Notch1en_US
dc.subjectMass Spectrometryen_US
dc.subjectHEK293 Cellsen_US
dc.subjectProtein Interaction Mapsen_US
dc.titleSystematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-05-26en_US
rioxxterms.versionofrecord10.1016/j.molcel.2020.06.029en_US
rioxxterms.licenseref.startdate2020-07-08en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfMolecular cellen_US
pubs.issue2en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.publication-statusPublisheden_US
pubs.volume79en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorDavey, Normanen_US


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