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Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients

The inactivation of parkin by mutation or post-translational modification contributes to dopaminergic neuronal death in Parkinson’s disease (PD). The substrates of parkin, FBP1 and AIMP2, are accumulated in the postmortem brains of PD patients, and it was recently suggested that these parkin substra...

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Autores principales: Jo, Areum, Lee, Yunjong, Park, Chi-Hu, Shin, Joo-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019889/
https://www.ncbi.nlm.nih.gov/pubmed/31878357
http://dx.doi.org/10.3390/jcm9010052
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author Jo, Areum
Lee, Yunjong
Park, Chi-Hu
Shin, Joo-Ho
author_facet Jo, Areum
Lee, Yunjong
Park, Chi-Hu
Shin, Joo-Ho
author_sort Jo, Areum
collection PubMed
description The inactivation of parkin by mutation or post-translational modification contributes to dopaminergic neuronal death in Parkinson’s disease (PD). The substrates of parkin, FBP1 and AIMP2, are accumulated in the postmortem brains of PD patients, and it was recently suggested that these parkin substrates transcriptionally activate deubiquitinase USP29. Herein, we newly identified 160 kDa myb-binding protein (MYBBP1A) as a novel substrate of USP29. Knockdown of parkin increased the level of AIMP2, leading to ultimately USP29 and MYBBP1A accumulation in SH-SY5Y cells. Notably, MYBBP1A was downregulated in the ventral midbrain (VM) of Aimp2 knockdown mice, whereas the upregulation of MYBBP1A was observed in the VM of inducible AIMP2 transgenic mice, as well as in the substantia nigra of sporadic PD patients. These results suggest that AIMP2 upregulates USP29 and MYBBP1A in the absence of parkin activity, contributing to PD pathogenesis.
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spelling pubmed-70198892020-03-09 Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients Jo, Areum Lee, Yunjong Park, Chi-Hu Shin, Joo-Ho J Clin Med Article The inactivation of parkin by mutation or post-translational modification contributes to dopaminergic neuronal death in Parkinson’s disease (PD). The substrates of parkin, FBP1 and AIMP2, are accumulated in the postmortem brains of PD patients, and it was recently suggested that these parkin substrates transcriptionally activate deubiquitinase USP29. Herein, we newly identified 160 kDa myb-binding protein (MYBBP1A) as a novel substrate of USP29. Knockdown of parkin increased the level of AIMP2, leading to ultimately USP29 and MYBBP1A accumulation in SH-SY5Y cells. Notably, MYBBP1A was downregulated in the ventral midbrain (VM) of Aimp2 knockdown mice, whereas the upregulation of MYBBP1A was observed in the VM of inducible AIMP2 transgenic mice, as well as in the substantia nigra of sporadic PD patients. These results suggest that AIMP2 upregulates USP29 and MYBBP1A in the absence of parkin activity, contributing to PD pathogenesis. MDPI 2019-12-24 /pmc/articles/PMC7019889/ /pubmed/31878357 http://dx.doi.org/10.3390/jcm9010052 Text en © 2019 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 Article
Jo, Areum
Lee, Yunjong
Park, Chi-Hu
Shin, Joo-Ho
Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title_full Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title_fullStr Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title_full_unstemmed Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title_short Deubiquitinase USP29 Governs MYBBP1A in the Brains of Parkinson’s Disease Patients
title_sort deubiquitinase usp29 governs mybbp1a in the brains of parkinson’s disease patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019889/
https://www.ncbi.nlm.nih.gov/pubmed/31878357
http://dx.doi.org/10.3390/jcm9010052
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