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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dc.contributor.author Zhang, Tao en_US
dc.contributor.author Dong, Kangyun en_US
dc.contributor.author Liang, Wei en_US
dc.contributor.author Xu, Daichao en_US
dc.contributor.author Xia, Hongguang en_US
dc.contributor.author Geng, Jiefei en_US
dc.contributor.author Najafov, Ayaz en_US
dc.contributor.author Liu, Min en_US
dc.contributor.author Li, Yanxia en_US
dc.contributor.author Han, Xiaoran en_US
dc.contributor.author Xiao, Juan en_US
dc.contributor.author Jin, Zhenzhen en_US
dc.contributor.author Peng, Ting en_US
dc.contributor.author Gao, Yang en_US
dc.contributor.author Cai, Yu en_US
dc.contributor.author Qi, Chunting en_US
dc.contributor.author Zhang, Qing en_US
dc.contributor.author Sun, Anyang en_US
dc.contributor.author Lipinski, Marta en_US
dc.contributor.author Zhu, Hong en_US
dc.contributor.author Xiong, Yue en_US
dc.contributor.author Pandolfi, Pier Paolo en_US
dc.contributor.author Li, He en_US
dc.contributor.author Yu, Qiang en_US
dc.contributor.author Yuan, Junying en_US
dc.date.accessioned 2015-06-02T12:22:28Z
dc.date.issued 2015 en_US
dc.identifier.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. en
dc.identifier.issn 2050-084X en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:16121075
dc.description.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 en
dc.language.iso en_US en
dc.publisher eLife Sciences Publications, Ltd en
dc.relation.isversionof doi:10.7554/eLife.06734 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421748/pdf/ en
dash.license LAA en_US
dc.subject autophagy en
dc.subject ubiquitination en
dc.subject GPCR en
dc.subject mouse en
dc.title G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal eLife en
dash.depositing.author Geng, Jiefei en_US
dc.date.available 2015-06-02T12:22:28Z

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