ArticleNature communications2024
The phosphatase DUSP22 inhibits UBR2-mediated K63-ubiquitination and activation of Lck downstream of TCR signalling.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- The dual-specificity phosphatase JSP1 regulates neutrophil adhesion via integrin-SRC signaling in vascular inflammation.The Journal of biological chemistry · 2026Article
- MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation.The Journal of clinical investigation · 2026Article
- DUSP22 dephosphorylates LGALS1 to enhance T cell-driven antitumor immunity.Journal for immunotherapy of cancer · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- Review
- PTPN22-CD45 dual phosphatase retrograde feedback enhances TCR signaling and autoimmunity.Science advances · 2025Article
- Identification of diabetes-related signatures as prognostic and therapeutic biomarkers in colon cancer.Discover oncology · 2025Article
- The role of UBR2 in triple-negative breast cancer and its implications for immune checkpoint blockade therapy.Discover oncology · 2025Article
- Combining antigen specific T-cells with T-cell engager therapy induces a molecular signature that favors T-cell fitness.Blood immunology & cellular therapy · 2025Article
- SOD2 is a regulator of proteasomal degradation promoting an adaptive cellular starvation response.Cell reports · 2025Article
- Serum JKAP as a potential prognostic biomarker in acute coronary syndrome patients undergoing percutaneous coronary intervention.Frontiers in cardiovascular medicine · 2025Article
- The role of ubiquitination in health and disease.MedComm · 2024Review
- Lck Function and Modulation: Immune Cytotoxic Response and Tumor Treatment More Than a Simple Event.Cancers · 2024Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DUSP22 is a dual-specificity phosphatase that inhibits T cell activation by inactivating the kinase Lck. Here we show that the E3 ubiquitin ligase UBR2 is a positive upstream regulator of Lck during T-cell activation. DUSP22 dephosphorylates UBR2 at specific Serine residues, leading to ubiquitin-mediated UBR2 degradation. UBR2 is also modified by the SCF E3 ubiquitin ligase complex via Lys48-linked ubiquitination at multiple Lysine residues. Single-cell RNA sequencing analysis and UBR2 loss of function experiments showed that UBR2 is a positive regulator of proinflammatory cytokine expression. Mechanistically, UBR2 induces Lys63-linked ubiquitination of Lck at Lys99 and Lys276 residues, followed by Lck Tyr394 phosphorylation and activation as part of TCR signalling. Inflammatory phenotypes induced by TCR-triggered Lck activation or knocking out DUSP22, are attenuated by genomic deletion of UBR2. UBR2-Lck interaction and Lck Lys63-linked ubiquitination are induced in the peripheral blood T cells of human SLE patients, which demonstrate the relevance of the UBR2-mediated regulation of inflammation to human pathology. In summary, we show here an important regulatory mechanism of T cell activation, which finetunes the balance between T cell response and aggravated inflammation.
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