Document Detail

Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.
MedLine Citation:
PMID:  20889974     Owner:  NLM     Status:  MEDLINE    
Parkin is an E3 ubiquitin ligase that mediates the ubiquitination of protein substrates. The mutations in the parkin gene can lead to a loss of function of parkin and cause autosomal recessive juvenile onset parkinsonism. Recently, parkin was reported to be involved in the regulation of mitophagy. Here, we identify the Bcl-2, an anti-apoptotic and autophagy inhibitory protein, as a substrate for parkin. Parkin directly binds to Bcl-2 via its C terminus and mediates the mono-ubiquitination of Bcl-2, which increases the steady-state levels of Bcl-2. Overexpression of parkin, but not its ligase-deficient forms, decreases autophagy marker LC3 conversion, whereas knockdown of parkin increases LC3 II levels. In HeLa cells, a parkin-deficient cell line, knockdown of parkin does not change LC3 conversion. Moreover, overexpression of parkin enhances the interactions between Bcl-2 and Beclin 1. Our results provide evidence that parkin mono-ubiquitinates Bcl-2 and regulates autophagy via Bcl-2.
Dong Chen; Feng Gao; Bin Li; Hongfeng Wang; Yuxia Xu; Cuiqing Zhu; Guanghui Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-29     Completed Date:  2010-12-30     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38214-23     Citation Subset:  IM    
Laboratory of Molecular Neuropathology, School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China.
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MeSH Terms
Apoptosis Regulatory Proteins / genetics,  metabolism
Dystonic Disorders / congenital,  genetics,  metabolism
HeLa Cells
Membrane Proteins / genetics,  metabolism
Microtubule-Associated Proteins / genetics,  metabolism
Protein Binding
Proto-Oncogene Proteins c-bcl-2 / genetics,  metabolism*
Ubiquitin-Protein Ligases / genetics,  metabolism*
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Membrane Proteins; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/light chain 3, human; EC Ligases; EC protein

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