G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L
文献类型：期刊论文
| 作者 | Zhang, Tao5; Dong, Kangyun5; Liang, Wei5; Xu, Daichao5; Xia, Hongguang6; Geng, Jiefei6; Najafov, Ayaz6; Liu, Min5; Li, Yanxia5; Han, Xiaoran7 |
| 刊名 | ELIFE
 |
| 出版日期 | 2015-03-30 |
| 卷号 | 4 |
| ISSN号 | 2050-084X |
| DOI | 10.7554/eLife.06734 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | GLYCOGEN-SYNTHASE KINASE-3-BETA ; DRUG DISCOVERY ; HIV-1 ENTRY ; PHOSPHORYLATION ; LIGASES ; INACTIVATION ; ADAPTERS ; COMPLEX ; RUBICON ; CELLS |
| 资助项目 | National Institute on Aging[R37 AG012859] ; National Institute on Aging[R01-AG047231] ; National Natural Science Foundation of China[31129004] ; Chinese Academy of Sciences[00000000] |
| WOS研究方向 | Life Sciences & Biomedicine - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000373786600001 |
| 出版者 | ELIFE SCIENCES PUBLICATIONS LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276596]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Yuan, Junying |
| 作者单位 | 1.Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Histol & Embryol, Wuhan 430074, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; 3.Harvard Univ, Beth Israel Deaconess Med Ctr, Canc Res Inst Beth,Med Sch, Beth Israel Deaconess Canc Ctr,Dept Med & Pathol, Boston, MA 02215 USA 4.Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA; 5.Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, 345 Lingling Lu, Shanghai 200032, Peoples R China; 6.Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA; 7.Fudan Univ, Inst Biomed Sci, Mol & Cell Biol Lab, Shanghai 200433, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Tao,Dong, Kangyun,Liang, Wei,et al. G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L[J]. ELIFE,2015,4. |
| APA | Zhang, Tao.,Dong, Kangyun.,Liang, Wei.,Xu, Daichao.,Xia, Hongguang.,...&Yuan, Junying.(2015).G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L.ELIFE,4. |
| MLA | Zhang, Tao,et al."G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L".ELIFE 4(2015). |
入库方式： OAI收割
来源：上海药物研究所
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