Parkin promotes proteasomal degradation of p62: implication of selective vulnerability of neuronal cells in the pathogenesis of Parkinson's disease
文献类型：期刊论文
| 作者 | Song, Pingping1; Li, Shanshan1; Wu, Hao2; Gao, Ruize1; Rao, Guanhua1; Wang, Dongmei3 ; Chen, Ziheng2; Ma, Biao1; Wang, Hongxia1; Sui, Nan3
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| 刊名 | PROTEIN & CELL
 |
| 出版日期 | 2016-02-01 |
| 卷号 | 7期号:2页码:114-129 |
| ISSN号 | 1674-800X |
| 关键词 | parkin sequestosome1/p62 ubiquitin substantia nigra |
| 英文摘要 | 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. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Cell Biology |
| 研究领域[WOS] | Cell Biology |
| 关键词[WOS] | AMYOTROPHIC-LATERAL-SCLEROSIS ; ALPHA-SYNUCLEIN ; DEFICIENT MICE ; MITOCHONDRIAL DEPOLARIZATION ; JUVENILE PARKINSONISM ; DAMAGED MITOCHONDRIA ; MOLECULAR PATHWAYS ; SEQUESTOSOME 1/P62 ; MEDIATE MITOPHAGY ; SQSTM1 MUTATIONS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000372541000005 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/19704]  |
| 专题 | 心理研究所_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. |
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来源：心理研究所
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