Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장용우 | - |
dc.date.accessioned | 2022-04-11T02:21:12Z | - |
dc.date.available | 2022-04-11T02:21:12Z | - |
dc.date.issued | 2020-08 | - |
dc.identifier.citation | NATURE CHEMICAL BIOLOGY, v. 16, no. 8, page. 876-886 | en_US |
dc.identifier.issn | 1552-4469 | - |
dc.identifier.issn | 1552-4450 | - |
dc.identifier.uri | https://www.nature.com/articles/s41589-020-0553-6 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/169865 | - |
dc.description.abstract | The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 angstrom resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21 degrees shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function. Prostaglandins PGE1 and PGA1 have neuroprotective effects by enhancing the transcriptional activity of Nurr1 by directly binding to its ligand-binding domain and upregulating their target genes implicated in Parkinson's disease. | en_US |
dc.description.sponsorship | We thank various members of the molecular neurobiology laboratory past and present who participated in the project. In particular, we thank B.-S. Han, H.-Y. Jung, J. Lee and J. Sung Koh for technical assistance. We also acknowledge the contribution of the scientists and staff on the PXII and PXIII (Paul Scherrer Institute, Switzerland) beamlines for their expert assistance during crystal data collection. This work was supported by NIH grant nos. NS070577 and NS084869 (to K.-S.K.), NRF-2018M3A9B5023055 grant (to C.-H.K.), Ministry of Education Singapore AcRF Tier 2 Grant (no. ARC55/16) and Tang Tieng See Advancement Fund (to H.S.Y.), and National Medical Research Council, Singapore (grant no. TCR/013-NNI/2014; to K.L.L. and H.S.Y.). | en_US |
dc.language.iso | en | en_US |
dc.publisher | NATURE PUBLISHING GROUP | en_US |
dc.subject | UNSATURATED FATTY-ACIDS | en_US |
dc.subject | RETINOID-X-RECEPTOR | en_US |
dc.subject | PARKINSONS-DISEASE | en_US |
dc.subject | NUCLEAR RECEPTORS | en_US |
dc.subject | DOPAMINERGIC-NEURONS | en_US |
dc.subject | PROSTAGLANDIN A(1) | en_US |
dc.subject | PPAR-GAMMA | en_US |
dc.subject | LIGAND | en_US |
dc.subject | NUR77 | en_US |
dc.subject | IDENTIFICATION | en_US |
dc.title | PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1038/s41589-020-0553-6 | - |
dc.relation.journal | NATURE CHEMICAL BIOLOGY | - |
dc.contributor.googleauthor | Rajan, Sreekanth | - |
dc.contributor.googleauthor | Jang, Yongwoo | - |
dc.contributor.googleauthor | Kim, Chun-Hyung | - |
dc.contributor.googleauthor | Kim, Woori | - |
dc.contributor.googleauthor | Toh, Hui Ting | - |
dc.contributor.googleauthor | Jeon, Jeha | - |
dc.contributor.googleauthor | Song, Bin | - |
dc.contributor.googleauthor | Serra, Aida | - |
dc.contributor.googleauthor | Lescar, Julien | - |
dc.contributor.googleauthor | Yoo, Jun Yeob | - |
dc.relation.code | 2020047422 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | ywjang | - |
dc.identifier.researcherID | Y-9854-2018 | - |
dc.identifier.orcid | https://orcid.org/0000-0003-1574-9009 | - |
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