Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.
Article Details
- CitationCopy to clipboard
Chen D, Gao F, Li B, Wang H, Xu Y, Zhu C, Wang G
Parkin mono-ubiquitinates Bcl-2 and regulates autophagy.
J Biol Chem. 2010 Dec 3;285(49):38214-23. doi: 10.1074/jbc.M110.101469. Epub 2010 Oct 2.
- PubMed ID
- 20889974 [ View in PubMed]
- Abstract
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.