PXD025319-1

PXD025319 is an original dataset announced via ProteomeXchange.

Title	Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation
Description	PTPN22, a modifier of T cell receptor signaling, and reactive oxygen species are major players in the regulation of chronic autoimmune diseases. As with all protein tyrosine phosphatases the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T cell-dependent inflammatory response due to enhanced TCR signaling and activation of T cells. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show in the mouse that the non-catalytic C129 residue of PTPN22 modulates its redox regulatory properties, and that oxidation-prone PTPN22 leads to increased severity in the development of T cell-dependent autoimmunity.
HostingRepository	PRIDE
AnnounceDate	2022-03-23
AnnouncementXML	Submission_2022-03-23_07:40:10.573.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Amir Ata Saei
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 07:59:25	ID requested
⏵ 1	2022-03-23 07:40:10	announced

Dataset with its publication pending

submitter keyword: Autoimmunity, PTPN22, reactive oxygen species, lymphocyte signaling

Prof. Roman. A. Zubarev
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	Roman.zubarev@ki.se
lab head
Amir Ata Saei
contact affiliation	Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	amirata.saei.dibavar@ki.se
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/2022/03/PXD025319

PRIDE project URI

• PRIDE
  1. PXD025319
     1. Label: PRIDE project
     2. Name: Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation