Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease

doi:10.1007/s13238-015-0230-9

PSYCH OpenIR > 健康与遗传心理学研究室

	Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease
	Song, Pingping 1; Li, Shanshan 1; Wu, Hao 2; Gao, Ruize 1; Rao, Guanhua 1; Wang, Dongmei3 ; Chen, Ziheng 2; Ma, Biao 1; Wang, Hongxia 1; Sui, Nan3 ; Deng, Haiteng 4; Zhang, Zhuohua 5; Tang, Tieshan 2; Tan, Zheng 2; Han, Zehan 6; Lu, Tieyuan 6; Zhu, Yushan 1; Chen, Quan 1,2
摘要	Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal cells in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
关键词	Parkin Sequestosome1/p62 Ubiquitin Substantia Nigra
	2016-02-01
语种	英语
DOI	10.1007/s13238-015-0230-9
发表期刊	PROTEIN & CELL
ISSN	1674-800X
卷号	7 期号:2 页码:114-129
期刊论文类型	Article
收录类别	SCI
WOS关键词	AMYOTROPHIC-LATERAL-SCLEROSIS ; ALPHA-SYNUCLEIN ; DEFICIENT MICE ; MITOCHONDRIAL DEPOLARIZATION ; JUVENILE PARKINSONISM ; DAMAGED MITOCHONDRIA ; MOLECULAR PATHWAYS ; SEQUESTOSOME 1/P62 ; MEDIATE MITOPHAGY ; SQSTM1 MUTATIONS
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000372541000005
资助机构	National Basic Research Program (973 Program) from MOST(2011CB910903) ; National Natural Science Foundation of China(81130045 ; 31471300 ; 31271529 ; 301520103904)
引用统计	被引频次：86[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://ir.psych.ac.cn/handle/311026/19704
专题	健康与遗传心理学研究室
作者单位	1.Nankai Univ, Tianjin Key Lab Prot Sci, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China 2.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China 4.Tsinghua Univ, Coll Life Sci, Beijing 100084, Peoples R China 5.Cent S Univ, Xiangya Med Sch, State Key Lab Med Genet, Changsha 410078, Hunan, Peoples R China 6.Tianjin Univ Sport, Dept Hlth & Sports Sci, Tianjin 300381, Peoples R China
推荐引用方式 GB/T 7714	Song, Pingping,Li, Shanshan,Wu, Hao,et al. Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease[J]. PROTEIN & CELL,2016,7(2):114-129.
APA	Song, Pingping.,Li, Shanshan.,Wu, Hao.,Gao, Ruize.,Rao, Guanhua.,...&Chen, Quan.(2016).Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease.PROTEIN & CELL,7(2),114-129.
MLA	Song, Pingping,et al."Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease".PROTEIN & CELL 7.2(2016):114-129.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
Parkin promotes prot（2388KB）	期刊论文	作者接受稿	开放获取	CC BY-NC-SA	浏览下载