ArticleNature communications2016
Tumour suppressor death-associated protein kinase targets cytoplasmic HIF-1α for Th17 suppression.
Article in Nature communications, 2016. 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, 24 citations in OpenAlex.
- Metabolic control of innate-like T cells.Nature reviews. Immunology · 2026Review
- Intermittent hypoxia: linkage between OSAS and epilepsy.Frontiers in pharmacology · 2023Review
- Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy.Frontiers in cell and developmental biology · 2021Review
- DAPK1 (death associated protein kinase 1) mediates mTORC1 activation and antiviral activities in CD8Cellular & molecular immunology · 2021Article
- HIF-2α is indispensable for regulatory T cell function.Nature communications · 2020Article
- Tumor suppressor death-associated protein kinase 1 inhibits necroptosis by p38 MAPK activation.Cell death & disease · 2020Article
- Molecular control of pathogenic Th17 cells in autoimmune diseases.International immunopharmacology · 2020Review
- HDAC6-specific inhibitor suppresses Th17 cell function via the HIF-1α pathway in acute lung allograft rejection in mice.Theranostics · 2020Article
- ERK Regulates HIF1α-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Expression and Functional Relevance of Death-Associated Protein Kinase in Human Drug-Resistant Epileptic Brain: Focusing on the Neurovascular Interface.Molecular neurobiology · 2019Article
- Regulation of the Expression of DAPK1 by SUMO Pathway.Biomolecules · 2019Article
- Tissue Immune Cells Fuel Obesity-Associated Inflammation in Adipose Tissue and Beyond.Frontiers in immunology · 2019Review
- Hypoxia-inducible factor 1 in clinical and experimental aortic aneurysm disease.Journal of vascular surgery · 2018Article
- Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death-associated protein kinase (DAPK) is a tumour suppressor. Here we show that DAPK also inhibits T helper 17 (Th17) and prevents Th17-mediated pathology in a mouse model of autoimmunity. We demonstrate that DAPK specifically downregulates hypoxia-inducible factor 1α (HIF-1α). In contrast to the predominant nuclear localization of HIF-1α in many cell types, HIF-1α is located in both the cytoplasm and nucleus in T cells, allowing for a cytosolic DAPK-HIF-1α interaction. DAPK also binds prolyl hydroxylase domain protein 2 (PHD2) and increases HIF-1α-PHD2 association. DAPK thereby promotes the proline hydroxylation and proteasome degradation of HIF-1α. Consequently, DAPK deficiency leads to excess HIF-1α accumulation, enhanced IL-17 expression and exacerbated experimental autoimmune encephalomyelitis. Additional knockout of HIF-1α restores the normal differentiation of Dapk(-/-) Th17 cells and prevents experimental autoimmune encephalomyelitis development. Our results reveal a mechanism involving DAPK-mediated degradation of cytoplasmic HIF-1α, and suggest that raising DAPK levels could be used for treatment of Th17-associated inflammatory diseases.
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