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dc.contributor.authorZhang, Taoen_US
dc.contributor.authorDong, Kangyunen_US
dc.contributor.authorLiang, Weien_US
dc.contributor.authorXu, Daichaoen_US
dc.contributor.authorXia, Hongguangen_US
dc.contributor.authorGeng, Jiefeien_US
dc.contributor.authorNajafov, Ayazen_US
dc.contributor.authorLiu, Minen_US
dc.contributor.authorLi, Yanxiaen_US
dc.contributor.authorHan, Xiaoranen_US
dc.contributor.authorXiao, Juanen_US
dc.contributor.authorJin, Zhenzhenen_US
dc.contributor.authorPeng, Tingen_US
dc.contributor.authorGao, Yangen_US
dc.contributor.authorCai, Yuen_US
dc.contributor.authorQi, Chuntingen_US
dc.contributor.authorZhang, Qingen_US
dc.contributor.authorSun, Anyangen_US
dc.contributor.authorLipinski, Martaen_US
dc.contributor.authorZhu, Hongen_US
dc.contributor.authorXiong, Yueen_US
dc.contributor.authorPandolfi, Pier Paoloen_US
dc.contributor.authorLi, Heen_US
dc.contributor.authorYu, Qiangen_US
dc.contributor.authorYuan, Junyingen_US
dc.date.accessioned2015-06-02T12:22:28Z
dc.date.issued2015en_US
dc.identifier.citationZhang, 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.issn2050-084Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:16121075
dc.description.abstractAutophagy 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.06734.001en
dc.language.isoen_USen
dc.publishereLife Sciences Publications, Ltden
dc.relation.isversionofdoi:10.7554/eLife.06734en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421748/pdf/en
dash.licenseLAAen_US
dc.subjectautophagyen
dc.subjectubiquitinationen
dc.subjectGPCRen
dc.subjectmouseen
dc.titleG-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14Len
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journaleLifeen
dash.depositing.authorGeng, Jiefeien_US
dc.date.available2015-06-02T12:22:28Z
dc.identifier.doi10.7554/eLife.06734*
dash.authorsorderedfalse
dash.contributor.affiliatedZhu, Hong
dash.contributor.affiliatedYuan, Junying
dash.contributor.affiliatedGeng, Jiefei
dash.contributor.affiliatedNajafov, Ayaz


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