PXD024935

PXD024935 is an original dataset announced via ProteomeXchange.

Title	Dissecting the functional selectivity of TGFβ signaling pathway components using genome engineered human organotypic skin models
Description	Transforming growth factor β (TGFβ) signaling is essential in cell growth and differentiation. Yet, the role of the individual TGFβ signaling components in human tissue homeostasis and transformation is still incompletely understood. Here we dissected the importance of the core components in the TGFβ signaling pathway by CRISPR/Cas9 genome editing of human keratinocytes. The edited keratinocytes were used for human organotypic skin cultures and global quantitative proteomics and phosphoproteomics by mass spectrometry. Characterization of cells and human organotypic skin tissues showed control of epithelial differentiation by Smad4-dependent TGF signaling through cell cycle regulation and ECM expression. In contrast, we found that the combined Smad4 dependent and independent pathways, governed by TGFβRII, controls epithelial homeostasis and prevents invasive growth by blocking epithelial inflammation and activation of p38 and ERK signaling. The study provides a framework for exploration of signaling pathways in human 3D tissue models and with global phosphoproteomics.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:52:45.665.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zilu Ye
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-03-23 03:09:53	ID requested
1	2023-02-09 13:36:10	announced
⏵ 2	2023-11-14 08:52:46	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: keratinocyte, proteomics, SMAD transcription factor,transforming growth factor beta (TGFβ), organotypic skin culture, CRISPR/Cas9, phosphoproteomics

Jesper Olsen
contact affiliation	Novo Nordisk Foundation Center for Protein Research, University of Copenhagen
contact email	jesper.olsen@cpr.ku.dk
lab head
Zilu Ye
contact affiliation	University of Copenhagen
contact email	yezlandss@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD024935
     1. Label: PRIDE project
     2. Name: Dissecting the functional selectivity of TGFβ signaling pathway components using genome engineered human organotypic skin models