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Biochem Biophys Res Commun. 2013 Oct 25. pii: S0006-291X(13)01767-1. doi: 10.1016/j.bbrc.2013.10.086. [Epub ahead of print]

The BAG2 Protein Stabilises PINK1 By Decreasing its Ubiquitination.

Author information

  • 1The Department of Neurology, Xiangya Hospital, Central South University, changsha, 410008 Hunan, People's Republic of China.
  • 2The Department of Neurology, Xiangya Hospital, Central South University, changsha, 410008 Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, 410008 Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, 410008 Hunan, People's Republic of China; Human Key Laboratory ofNeurodegenerative Disorders,Central South University, Changsha, 410008 Hunan, People's Republic of China.
  • 3Laboratoryof Molecular Neuropathology, Department of Pharmacology, Soochow UniversityCollege of Pharmaceutical Sciences, Suzhou, Jiangsu 201203, China.
  • 4The Department of Neurology, Xiangya Hospital, Central South University, changsha, 410008 Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, 410008 Hunan, People's Republic of China; Human Key Laboratory ofNeurodegenerative Disorders,Central South University, Changsha, 410008 Hunan, People's Republic of China.
  • 5The Department of Neurology, Xiangya Hospital, Central South University, changsha, 410008 Hunan, People's Republic of China; State Key Laboratory of Medical Genetics, Changsha, 410008 Hunan, People's Republic of China; Neurodegenerative Disorders Research Center, Central South University, Changsha, 410008 Hunan, People's Republic of China; Human Key Laboratory ofNeurodegenerative Disorders,Central South University, Changsha, 410008 Hunan, People's Republic of China. Electronic address: guojifeng2003@163.com.

Abstract

Mutations in the PTEN-induced putative kinase 1 (PINK1) gene cause an autosomal recessive form of Parkinson disease (PD). Thus far, little is known about what can regulate the ubiquitin proteasome pathway of PINK1. Here, we reportBAG2(Bcl-2-associated athanogene family protein 2), a member of the BAG family, which directly binds with and stabilises PINK1 by decreasing its ubiquitination. Moreover, we found that BAG2 also binds with the pathogenic R492X PINK1 mutationdirectly and more tightly.Moreover, BAG2 stabilises the R492X PINK1 mutation by decreasing its ubiquitination to a greater extent than the wild-type species. Our data correlate BAG2 to PINK1 for the first time, strengthening the important role of BAG2 in PD-related neurodegeneration.

Copyright © 2013. Published by Elsevier Inc.

KEYWORDS:

BAG; BAG2; Bcl-2-associated athanogene 2; Bcl-2associated athanogene; DMEM; Dulbecco’s modified Eagle’s medium; Mutations in PTEN-inducedkinase 1; PD; PINK1; Parkinsondisease; Parkinson’s disease; Protein degradation; UPS; Ubiquitination; ubiquitin proteasome system

PMID:
24513209
[PubMed - as supplied by publisher]
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