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PXD003281

PXD003281 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleA protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis
DescriptionEpidermal homeostasis depends on a balance between stem cell renewal and terminal differentiation. The transition between the two cell states,termed commitment, is poorly understood. Here we characterise commitment by integrating transcriptomic and proteomic data from disaggregated primary human keratinocytes held in suspension to induce differentiation. Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA – promote differentiation by negatively regulating ERK MAPK and positively regulating AP1 transcription factors. Conversely, DUSP10 expression antagonises commitment. The phosphatases form a dynamic network of transient positive and negative interactions that change over time, with DUSP6 predominating at commitment. Boolean network modelling identifies a mandatory switch between two stable states (stem and differentiated) via an unstable (committed) state. Phosphatase expression is also spatially regulated in vivo and in vitro. We conclude that an auto-regulatory phosphatase network maintains epidermal homeostasis by controlling the onset and duration of commitment.
HostingRepositoryPRIDE
AnnounceDate2017-10-18
AnnouncementXMLSubmission_2019-02-12_07:55:36.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVackar Afzal
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListdeaminated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02015-12-07 00:25:43ID requested
12017-10-18 23:36:35announced
22019-02-12 07:55:38announcedUpdated publication reference for PubMed record(s): 29043977.
Publication List
Mishra A, Oulès B, Pisco AO, Ly T, Liakath-Ali K, Walko G, Viswanathan P, Tihy M, Nijjher J, Dunn SJ, Lamond AI, Watt FM, A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis. Elife, 6():(2017) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: Human, Keratinocytes, U2OS, PKC, Timecourse
Contact List
Angus Lamond
contact affiliationPrinciple Investigator
contact emailailamond@dundee.ac.uk
lab head
Vackar Afzal
contact affiliationSchool of Life Sciences
contact emailv.z.afzal@dundee.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
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