Parkin mono-ubiquitinates Bcl-2 and regulates autophagy |
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Authors: | Chen Dong Gao Feng Li Bin Wang Hongfeng Xu Yuxia Zhu Cuiqing Wang Guanghui |
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Institution: | 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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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. |
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Keywords: | Autophagy E3 Ubiquitin Ligase Mitochondria Parkinson Disease Ubiquitination Bcl-2 Parkin |
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