ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle
文献类型:期刊论文
作者 | Li, Zhiyuan1![]() ![]() |
刊名 | PLOS BIOLOGY
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出版日期 | 2020-06-01 |
卷号 | 18 |
ISSN号 | 1544-9173 |
DOI | 10.1371/journal.pbio.3000288 |
通讯作者 | Li, Zhiyuan(xinzhang@hmfl.ac.cn) ; Zhang, Xin(lizhiyuan@hmfl.ac.cn) |
英文摘要 | Unc-51-like autophagy activating kinase 1 (ULK1)-autophagy-related 13 (ATG13) is the most upstream autophagy initiation complex that is phosphorylated by mammalian target-of-rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK) to induce autophagy in asynchronous conditions. However, their phospho-regulation and functions in mitosis and cell cycle remain unknown. Here we show that ULK1-ATG13 complex is differentially regulated throughout the cell cycle, especially in mitosis, in which both ULK1 and ATG13 are highly phosphorylated by the key cell cycle machinery cyclin-dependent kinase 1 (CDK1)/cyclin B. Combining mass spectrometry and site-directed mutagenesis, we found that CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression. Moreover, double knockout (DKO) of ULK1 and ATG13 could block cell cycle progression and significantly decrease cancer cell proliferation in cell line and mouse models. Our results not only bridge the mutual regulation between the core machinery of autophagy and mitosis but also illustrate the positive function of ULK1-ATG13 and their phosphorylation by CDK1 in mitotic autophagy regulation. |
WOS关键词 | ACTIVATED PROTEIN-KINASE ; CHROMOSOME CONGRESSION ; AURORA-B ; PHOSPHORYLATION ; ULK1 ; INHIBITOR ; COMPLEX ; IDENTIFICATION ; AMPK ; DISSOCIATION |
资助项目 | National Key Research and Development Program of China[2016YFA0400900] ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology[2016FXCX004] ; Key Program of 13th five-year plan ; CASHIPS[KP2017-26] ; CASHIPS Director's Fund[YZJJ201704] ; CASHIPS Director's Fund[YZJJ2019QN17] ; National Natural Science Foundation of China[31900508] ; Anhui Natural Science Foundation[1908085MC88] |
WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics |
语种 | 英语 |
WOS记录号 | WOS:000544030100001 |
出版者 | PUBLIC LIBRARY SCIENCE |
资助机构 | National Key Research and Development Program of China ; Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology ; Key Program of 13th five-year plan ; CASHIPS ; CASHIPS Director's Fund ; National Natural Science Foundation of China ; Anhui Natural Science Foundation |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/92847] ![]() |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Li, Zhiyuan; Zhang, Xin |
作者单位 | 1.Chinese Acad Sci, Hefei Inst Phys Sci, High Field Magnet Lab, Key Lab High Magnet Field & Ion Beam Phys Biol, Hefei, Anhui, Peoples R China 2.Anhui Univ, Inst Phys Sci & Informat Technol, Hefei, Anhui, Peoples R China |
推荐引用方式 GB/T 7714 | Li, Zhiyuan,Tian, Xiaofei,Ji, Xinmiao,et al. ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle[J]. PLOS BIOLOGY,2020,18. |
APA | Li, Zhiyuan.,Tian, Xiaofei.,Ji, Xinmiao.,Wang, Junjun.,Chen, Hanxiao.,...&Zhang, Xin.(2020).ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle.PLOS BIOLOGY,18. |
MLA | Li, Zhiyuan,et al."ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle".PLOS BIOLOGY 18(2020). |
入库方式: OAI收割
来源:合肥物质科学研究院
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