https://scholars.lib.ntu.edu.tw/handle/123456789/416283
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chou, Ting-Fang | en_US |
dc.contributor.author | Chuang, Ya-Ting | en_US |
dc.contributor.author | Hsieh, Wan-Chen | en_US |
dc.contributor.author | Chang, Pei-Yun | en_US |
dc.contributor.author | Liu, Hsin-Yu | en_US |
dc.contributor.author | Mo, Shu-Ting | en_US |
dc.contributor.author | Hsu, Tzu-Sheng | en_US |
dc.contributor.author | SHI-CHUEN MIAW | en_US |
dc.contributor.author | Chen, Ruey-Hwa | en_US |
dc.contributor.author | Kimchi, Adi | en_US |
dc.contributor.author | Lai, Ming-Zong | en_US |
dc.creator | Chou, Ting-Fang;Chuang, Ya-Ting;Hsieh, Wan-Chen;Chang, Pei-Yun;Liu, Hsin-Yu;Mo, Shu-Ting;Hsu, Tzu-Sheng;Shi-Chuen Miaw;Chen, Ruey-Hwa;Kimchi, Adi;Lai, Ming-Zong | - |
dc.date.accessioned | 2019-08-06T05:24:43Z | - |
dc.date.available | 2019-08-06T05:24:43Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84975516240&doi=10.1038%2fncomms11904&partnerID=40&md5=455e5859d18aaa336bb9f3b3b30c6d00 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/416283 | - |
dc.description.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. | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.relation.ispartof | Nature communications | en_US |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | death associated protein kinase; hypoxia inducible factor 1alpha; interleukin 17; procollagen proline 2 oxoglutarate 4 dioxygenase; proline; proteasome; Dapk1 protein, mouse; death associated protein kinase; Egln1 protein, mouse; Hif1a protein, mouse; hypoxia inducible factor 1alpha; hypoxia inducible factor proline dioxygenase; interleukin 17; myelin oligodendrocyte glycoprotein; myelin oligodendrocyte glycoprotein (35-55); peptide fragment; pertussis toxin; proline; proteasome; small interfering RNA; cytoplasm; degradation; differentiation; disease; enzyme; enzyme activity; pathology; protein; rodent; tumor; animal cell; animal experiment; Article; autoimmunity; cell differentiation; cell nucleus; cells by body anatomy; cellular distribution; controlled study; cytoplasm; down regulation; experimental autoimmune encephalomyelitis; female; hydroxylation; male; mouse; nonhuman; protein binding; protein degradation; protein expression; protein protein interaction; Th17 cell; animal; antagonists and inhibitors; deficiency; drug effect; experimental autoimmune encephalomyelitis; gene expression regulation; genetics; HEK293 cell line; HeLa cell line; human; immunology; Jurkat cell line; knockout mouse; metabolism; pathology; regulatory T lymphocyte; signal transduction; Th17 cell; Animals; Death-Associated Protein Kinases; Encephalomyelitis, Autoimmune, Experimental; Gene Expression Regulation; HEK293 Cells; HeLa Cells; Humans; Hydroxylation; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-Inducible Factor-Proline Dioxygenases; Interleukin-17; Jurkat Cells; Mice; Mice, Knockout; Myelin-Oligodendrocyte Glycoprotein; Peptide Fragments; Pertussis Toxin; Proline; Proteasome Endopeptidase Complex; Proteolysis; RNA, Small Interfering; Signal Transduction; T-Lymphocytes, Regulatory; Th17 Cells | - |
dc.title | Tumour suppressor death-associated protein kinase targets cytoplasmic HIF-1α for Th17 suppression | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1038/ncomms11904 | - |
dc.identifier.pmid | 27312851 | - |
dc.identifier.scopus | 2-s2.0-84975516240 | - |
dc.identifier.isi | WOS:000379080400001 | - |
dc.identifier.url | https://api.elsevier.com/content/abstract/scopus_id/84975516240 | - |
dc.relation.journalvolume | 7 | en_US |
dc.relation.journalissue | 1 | en_US |
item.openairetype | journal article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.fulltext | no fulltext | - |
item.grantfulltext | none | - |
crisitem.author.dept | Immunology | - |
crisitem.author.orcid | 0000-0003-1347-9367 | - |
crisitem.author.parentorg | College of Medicine | - |
Appears in Collections: | 免疫學研究所 |
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