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Review

Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models

1
Department of Pathological Cell Biology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
2
Department of Stress Response Science, Center for Advanced Medical Research, Graduate School of Medicine, Hirosaki University, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan
3
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan
4
Department of Molecular and Chemical Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1202; https://doi.org/10.3390/ijms21041202
Received: 22 January 2020 / Revised: 7 February 2020 / Accepted: 9 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Animal Models of Parkinson's Disease and Related Disorders)
Parkinson’s disease (PD) is a common neurodegenerative disorder. Recent identification of genes linked to familial forms of PD has revealed that post-translational modifications, such as phosphorylation and ubiquitination of proteins, are key factors in disease pathogenesis. In PD, E3 ubiquitin ligase Parkin and the serine/threonine-protein kinase PTEN-induced kinase 1 (PINK1) mediate the mitophagy pathway for mitochondrial quality control via phosphorylation and ubiquitination of their substrates. In this review, we first focus on well-characterized PINK1 phosphorylation motifs. Second, we describe our findings concerning relationships between Parkin and HtrA2/Omi, a protein involved in familial PD. Third, we describe our findings regarding inhibitory PAS (Per/Arnt/Sim) domain protein (IPAS), a member of PINK1 and Parkin substrates, involved in neurodegeneration during PD. IPAS is a dual-function protein involved in transcriptional repression of hypoxic responses and the pro-apoptotic activities. View Full-Text
Keywords: Parkinson’s disease; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Parkin; PINK1; HtrA2/Omi; IPAS Parkinson’s disease; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP); Parkin; PINK1; HtrA2/Omi; IPAS
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MDPI and ACS Style

Torii, S.; Kasai, S.; Yoshida, T.; Yasumoto, K.-i.; Shimizu, S. Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models. Int. J. Mol. Sci. 2020, 21, 1202. https://doi.org/10.3390/ijms21041202

AMA Style

Torii S, Kasai S, Yoshida T, Yasumoto K-i, Shimizu S. Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models. International Journal of Molecular Sciences. 2020; 21(4):1202. https://doi.org/10.3390/ijms21041202

Chicago/Turabian Style

Torii, Satoru; Kasai, Shuya; Yoshida, Tatsushi; Yasumoto, Ken-ichi; Shimizu, Shigeomi. 2020. "Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models" Int. J. Mol. Sci. 21, no. 4: 1202. https://doi.org/10.3390/ijms21041202

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