USP14 regulates autophagy by suppressing K63 ubiquitination of Beclin 1
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Author
Xu, Daichao
Shan, Bing
Sun, Huawang
Xiao, Juan
Zhu, Kezhou
Xie, Xingxing
Li, Xingyan
Liang, Wei
Lu, Xiaojuan
Qian, Lihui
Yuan, Junying
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https://doi.org/10.1101/gad.285122.116Metadata
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Xu, Daichao, Bing Shan, Huawang Sun, Juan Xiao, Kezhou Zhu, Xingxing Xie, Xingyan Li, et al. 2016. “USP14 Regulates Autophagy by Suppressing K63 Ubiquitination of Beclin 1.” Genes & Development 30 (15): 1718–30. https://doi.org/10.1101/gad.285122.116.Abstract
The ubiquitin proteasome system (UPS) and autophagy are two major intracellular degradative mechanisms that mediate the turnover of complementary repertoires of intracellular proteomes. Simultaneously activating both UPS and autophagy might provide a powerful strategy for the clearance of misfolded proteins. However, it is not clear whether UPS and autophagy can be controlled by a common regulatory mechanism. K48 deubiquitination by USP14 is known to inhibit UPS. Here we show that USP14 regulates autophagy by negatively controlling K63 ubiquitination of Beclin 1. Furthermore, we show that activation of USP14 by Akt-mediated phosphorylation provides a mechanism for Akt to negatively regulate autophagy by promoting K63 deubiquitination. Our study suggests that Akt-regulated USP14 activity modulates both proteasomal degradation and autophagy through controlling K48 and K63 ubiquitination, respectively. Therefore, regulation of USP14 provides a mechanism for Akt to control both proteasomal and autophagic degradation. We propose that inhibition of USP14 may provide a strategy to promote both UPS and autophagy for developing novel therapeutics targeting neurodegenerative diseases.Terms of Use
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