title: DJ-1/PARK7, But Not Its L166P Mutant Linked to Autosomal Recessive Parkinsonism, Modulates the Transcriptional Activity of the Orphan Nuclear Receptor Nurr1 In Vitro and In Vivo.
abstract: Although mutations of DJ-1 have been linked to autosomal recessive Parkinsonism for years, its physiological function and the pathological mechanism of its mutants are not well understood. We report for the first time that exogenous application of DJ-1, but not its L166P mutant, enhances the nuclear translocation and the transcriptional activity of Nurr1, a transcription factor essential for dopaminergic neuron development and maturation, both in vitro and in vivo. Knockdown of DJ-1 attenuates Nurr1 activity. Further investigation showed that signaling of Raf/MEK/ERK MAPKs is involved in this regulatory process and that activation induced by exogenous DJ-1 is antagonized by U0126, an ERK pathway inhibitor, indicating that DJ-1 modulates Nurr1 activity via the Raf/MEK/ERK pathway. Our findings shed light on the novel function of DJ-1 to enhance Nurr1 activity and provide the first insight into the molecular mechanism by which DJ-1 enhances Nurr1 activity.
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Sun
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China.
authors.forename: Huanying
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Center of Parkinson's Disease, Beijing Institute for Brain Disorders, Department of Neurobiology, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, Beijing, 100069, China. huiyang@ccmu.edu.cn.|Center of Parkinson's Disease, Beijing Institute of Brain Disorders, Capital Medical University, Beijing Center of Neural Regeneration and Repair, Key Laboratory for Neurodegenerative Diseases of the Ministry of Education, 10 You an men Wai, Xitoutiao, Beijing, 100069, China. huiyang@ccmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D050505:Mutant Proteins / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D000071617:Protein Deglycase DJ-1 / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D050505:Mutant Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D000071617:Protein Deglycase DJ-1
keywords: DJ-1; Nurr1; Parkinson’s disease; Signal transduction; Transcription factor