G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L

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G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L

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Title: G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L
Author: Zhang, Tao; Dong, Kangyun; Liang, Wei; Xu, Daichao; Xia, Hongguang; Geng, Jiefei; Najafov, Ayaz; Liu, Min; Li, Yanxia; Han, Xiaoran; Xiao, Juan; Jin, Zhenzhen; Peng, Ting; Gao, Yang; Cai, Yu; Qi, Chunting; Zhang, Qing; Sun, Anyang; Lipinski, Marta; Zhu, Hong; Xiong, Yue; Pandolfi, Pier Paolo; Li, He; Yu, Qiang; Yuan, Junying

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhang, T., K. Dong, W. Liang, D. Xu, H. Xia, J. Geng, A. Najafov, et al. 2015. “G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L.” eLife 4 (1): e06734. doi:10.7554/eLife.06734. http://dx.doi.org/10.7554/eLife.06734.
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Abstract: Autophagy is an important intracellular catabolic mechanism involved in the removal of misfolded proteins. Atg14L, the mammalian ortholog of Atg14 in yeast and a critical regulator of autophagy, mediates the production PtdIns3P to initiate the formation of autophagosomes. However, it is not clear how Atg14L is regulated. In this study, we demonstrate that ubiquitination and degradation of Atg14L is controlled by ZBTB16-Cullin3-Roc1 E3 ubiquitin ligase complex. Furthermore, we show that a wide range of G-protein-coupled receptor (GPCR) ligands and agonists regulate the levels of Atg14L through ZBTB16. In addition, we show that the activation of autophagy by pharmacological inhibition of GPCR reduces the accumulation of misfolded proteins and protects against behavior dysfunction in a mouse model of Huntington's disease. Our study demonstrates a common molecular mechanism by which the activation of GPCRs leads to the suppression of autophagy and a pharmacological strategy to activate autophagy in the CNS for the treatment of neurodegenerative diseases. DOI: http://dx.doi.org/10.7554/eLife.06734.001
Published Version: doi:10.7554/eLife.06734
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421748/pdf/
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Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:16121075
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