PXD043457

PXD043457 is an original dataset announced via ProteomeXchange.

Title	The phosphatase DUSP22/JKAP inhibits UBR2-mediated K63-ubiquitination and activation of Lck in TCR signaling
Description	DUSP22 (also named JKAP) is a dual-specificity phosphatase that inhibits T cell activation. Here we identified the E3 ubiquitin ligase UBR2 as an upstream activator of Lck during T-cell activation. JKAP dephosphorylated UBR2 at two residues, leading to ubiquitin-mediated UBR2 degradation. The SCF (SKP1-CUL1-βTrCP) complex induced UBR2 Lys48-linked ubiquitination at three lysine residues. Moreover, single-cell RNA sequencing analysis and UBR2 knockout showed that UBR2 increased proinflammatory cytokines. Remarkably, UBR2 induced Lys63-linked ubiquitination of Lck at two lysine residues and subsequent Lck Tyr394 phosphorylation/activation in TCR signaling. Conversely, TCR-induced Lck activation and JKAP knockout-enhanced inflammatory phenotypes were attenuated by UBR2 knockout. Consistently, the UBR2- Lck interaction and Lck Lys63-linked ubiquitination were induced in peripheral blood T cells of human SLE patients. Collectively, UBR2 protein stability and UBR2-induced Lck ubiquitination/activation are inhibited by JKAP, leading to attenuation of T-cell activation and T-cell-mediated inflammation.
HostingRepository	PRIDE
AnnounceDate	2024-01-16
AnnouncementXML	Submission_2024-01-16_08:04:47.473.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ying chun shih
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-02 22:24:49	ID requested
1	2024-01-04 01:36:19	announced
⏵ 2	2024-01-16 08:04:47	announced	2024-01-16: Updated project metadata.

10.1038/S41467-024-44843-W;

submitter keyword: Human Jurkat T cells

Tse-Hua Tan
contact affiliation	Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas
contact email	ttan@nhri.edu.tw
lab head
ying chun shih
contact affiliation	NHRI
contact email	ycs0979151611ycs@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD043457
     1. Label: PRIDE project
     2. Name: The phosphatase DUSP22/JKAP inhibits UBR2-mediated K63-ubiquitination and activation of Lck in TCR signaling