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dc.contributor.authorWigington, CP
dc.contributor.authorRoy, J
dc.contributor.authorDamle, NP
dc.contributor.authorYadav, VK
dc.contributor.authorBlikstad, C
dc.contributor.authorResch, E
dc.contributor.authorWong, CJ
dc.contributor.authorMackay, DR
dc.contributor.authorWang, JT
dc.contributor.authorKrystkowiak, I
dc.contributor.authorBradburn, DA
dc.contributor.authorTsekitsidou, E
dc.contributor.authorHong, SH
dc.contributor.authorKaderali, MA
dc.contributor.authorXu, S-L
dc.contributor.authorStearns, T
dc.contributor.authorGingras, A-C
dc.contributor.authorUllman, KS
dc.contributor.authorIvarsson, Y
dc.contributor.authorDavey, NE
dc.contributor.authorCyert, MS
dc.date.accessioned2020-09-30T11:07:08Z
dc.date.issued2020-07-08
dc.identifier.citationMolecular cell, 2020, 79 (2), pp. 342 - 358.e12
dc.identifier.issn1097-2765
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4095
dc.identifier.eissn1097-4164
dc.identifier.doi10.1016/j.molcel.2020.06.029
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 2+ -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 2+ 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 2+ and CN signaling and demonstrates synergy between experimental and computational methods, establishing a blueprint for examining SLiM-based networks.
dc.formatPrint-Electronic
dc.format.extent342 - 358.e12
dc.languageeng
dc.language.isoeng
dc.subjectHela Cells
dc.subjectCentrosome
dc.subjectHumans
dc.subjectSaccharomyces cerevisiae
dc.subjectPhosphoric Monoester Hydrolases
dc.subjectCalcineurin
dc.subjectNuclear Pore Complex Proteins
dc.subjectSaccharomyces cerevisiae Proteins
dc.subjectProteome
dc.subjectBiotinylation
dc.subjectSignal Transduction
dc.subjectAmino Acid Motifs
dc.subjectActive Transport, Cell Nucleus
dc.subjectPhosphorylation
dc.subjectComputer Simulation
dc.subjectReceptor, Notch1
dc.subjectMass Spectrometry
dc.subjectHEK293 Cells
dc.subjectProtein Interaction Maps
dc.titleSystematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.
dc.typeJournal Article
dcterms.dateAccepted2020-05-26
rioxxterms.versionofrecord10.1016/j.molcel.2020.06.029
rioxxterms.licenseref.startdate2020-07-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular cell
pubs.issue2
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.volume79
pubs.embargo.termsNot known
dc.contributor.icrauthorDavey, Normanen


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