PXD019272

PXD019272 is an original dataset announced via ProteomeXchange.

Title	Itch attenuates CD4 T cell proliferation in mice by limiting WBP2 protein stability
Description	To mount an anti-pathogen response, CD4 T cells must undergo rapid cell proliferation. However, poorly controlled expansion can result in diseases such as autoimmunity. One important regulator of T cell activity is the E3 ubiquitin ligase Itch. Itch deficient patients suffer from extensive autoinflammation. Similarly, Itch deficient mice exhibit inflammation characterized by high numbers of activated CD4 T cells. While the role of Itch in limiting CD4 T cell cytokine production has been extensively studied, it is less clear whether and how Itch regulates proliferation of these cells. We determined that Itch deficient CD4 T cells are hyperproliferative in vitro and in vivo, due to increased S phase entry. Whole cell proteomics analysis of Itch deficient primary mouse CD4 T cells revealed increased abundance of the -catenin co-activator WW domain binding protein 2 (WBP2). Furthermore, Itch deficient cells demonstrate increased WBP2 protein stability, and Itch and WBP2 interact in CD4 T cells. Knockdown of WBP2 in CD4 T cells caused reduced proliferation. Together, our data support that Itch attenuates CD4 T cell proliferation by promoting WBP2 degradation. This study identifies novel roles for Itch and WBP2 in regulating CD4 T cell proliferation, providing insight into how Itch may prevent inflammation.
HostingRepository	PRIDE
AnnounceDate	2021-01-07
AnnouncementXML	Submission_2021-01-07_00:31:33.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-18 17:01:42	ID requested
⏵ 1	2021-01-07 00:31:34	announced

Field NS, Elbulok OA, Dybas JM, Moser EK, Dar AA, Spruce LA, Fazelinia H, Seeholzer SH, Oliver PM, Itch attenuates CD4 T-cell proliferation in mice by limiting WBP2 protein stability. Eur J Immunol, 50(10):1468-1483(2020) [pubmed]

submitter keyword: proliferation, cell cycle, autoinflammation, E3 ubiquitin ligase

Steven H. Seeholzer
contact affiliation	Director of Proteomics Core Facility, Children's Hospital of Philadelphia, Philadelphia, PA USA
contact email	seeholzer@email.chop.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2021/01/PXD019272

PRIDE project URI

• PRIDE
  1. PXD019272
     1. Label: PRIDE project
     2. Name: Itch attenuates CD4 T cell proliferation in mice by limiting WBP2 protein stability