Cargando…

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

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 liga...

Descripción completa

Detalles Bibliográficos
Autores principales: Torii, Satoru, Kasai, Shuya, Yoshida, Tatsushi, Yasumoto, Ken-ichi, Shimizu, Shigeomi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072767/
https://www.ncbi.nlm.nih.gov/pubmed/32054064
http://dx.doi.org/10.3390/ijms21041202
_version_ 1783506483253608448
author Torii, Satoru
Kasai, Shuya
Yoshida, Tatsushi
Yasumoto, Ken-ichi
Shimizu, Shigeomi
author_facet Torii, Satoru
Kasai, Shuya
Yoshida, Tatsushi
Yasumoto, Ken-ichi
Shimizu, Shigeomi
author_sort Torii, Satoru
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7072767
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70727672020-03-19 Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models Torii, Satoru Kasai, Shuya Yoshida, Tatsushi Yasumoto, Ken-ichi Shimizu, Shigeomi Int J Mol Sci Review 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. MDPI 2020-02-11 /pmc/articles/PMC7072767/ /pubmed/32054064 http://dx.doi.org/10.3390/ijms21041202 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Torii, Satoru
Kasai, Shuya
Yoshida, Tatsushi
Yasumoto, Ken-ichi
Shimizu, Shigeomi
Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title_full Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title_fullStr Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title_full_unstemmed Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title_short Mitochondrial E3 Ubiquitin Ligase Parkin: Relationships with Other Causal Proteins in Familial Parkinson’s Disease and Its Substrate-Involved Mouse Experimental Models
title_sort mitochondrial e3 ubiquitin ligase parkin: relationships with other causal proteins in familial parkinson’s disease and its substrate-involved mouse experimental models
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072767/
https://www.ncbi.nlm.nih.gov/pubmed/32054064
http://dx.doi.org/10.3390/ijms21041202
work_keys_str_mv AT toriisatoru mitochondriale3ubiquitinligaseparkinrelationshipswithothercausalproteinsinfamilialparkinsonsdiseaseanditssubstrateinvolvedmouseexperimentalmodels
AT kasaishuya mitochondriale3ubiquitinligaseparkinrelationshipswithothercausalproteinsinfamilialparkinsonsdiseaseanditssubstrateinvolvedmouseexperimentalmodels
AT yoshidatatsushi mitochondriale3ubiquitinligaseparkinrelationshipswithothercausalproteinsinfamilialparkinsonsdiseaseanditssubstrateinvolvedmouseexperimentalmodels
AT yasumotokenichi mitochondriale3ubiquitinligaseparkinrelationshipswithothercausalproteinsinfamilialparkinsonsdiseaseanditssubstrateinvolvedmouseexperimentalmodels
AT shimizushigeomi mitochondriale3ubiquitinligaseparkinrelationshipswithothercausalproteinsinfamilialparkinsonsdiseaseanditssubstrateinvolvedmouseexperimentalmodels