PXD003281

PXD003281 is an original dataset announced via ProteomeXchange.

Title	A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis
Description	Epidermal 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.
HostingRepository	PRIDE
AnnounceDate	2017-10-18
AnnouncementXML	Submission_2019-02-12_07:55:36.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Vackar Afzal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deaminated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-12-07 00:25:43	ID requested
1	2017-10-18 23:36:35	announced
⏵ 2	2019-02-12 07:55:38	announced	Updated publication reference for PubMed record(s): 29043977.

Mishra A, Oul, è, s 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]

curator keyword: Biological

submitter keyword: Human, Keratinocytes, U2OS, PKC, Timecourse

Angus Lamond
contact affiliation	Principle Investigator
contact email	ailamond@dundee.ac.uk
lab head
Vackar Afzal
contact affiliation	School of Life Sciences
contact email	v.z.afzal@dundee.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/10/PXD003281

PRIDE project URI

• PRIDE
  1. PXD003281
     1. Label: PRIDE project
     2. Name: A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis