| Parkin mono-ubiquitinates Bcl-2 and regulates autophagy. | |
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MedLine Citation:
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PMID: 20889974 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Dong Chen; Feng Gao; Bin Li; Hongfeng Wang; Yuxia Xu; Cuiqing Zhu; Guanghui Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-02 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-29 Completed Date: 2010-12-30 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 38214-23 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Neuropathology, School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Regulatory Proteins
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genetics,
metabolism Autophagy* Dystonic Disorders / congenital, genetics, metabolism HeLa Cells Humans Membrane Proteins / genetics, metabolism Microtubule-Associated Proteins / genetics, metabolism Protein Binding Proto-Oncogene Proteins c-bcl-2 / genetics, metabolism* Ubiquitin-Protein Ligases / genetics, metabolism* Ubiquitination* |
| Chemical | |
Reg. No./Substance:
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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 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/parkin protein |
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