Global and Site-Specific Effect of Phosphorylation on Protein Turnover

doi:10.1016/j.devcel.2020.10.025

	Global and Site-Specific Effect of Phosphorylation on Protein Turnover
	Wu, Chongde 1; Ba, Qian 1; Lu, Dayun 2,4; Li, Wenxue 1; Salovska, Barbora 1,8; Hou, Pingfu 1; Mueller, Torsten 3; Rosenberger, George 5; Gao, Erli 1; Di, Yi 1
刊名	DEVELOPMENTAL CELL
	2021-01-11
卷号	56 期号:1 页码:111-+
ISSN号	1534-5807
DOI	10.1016/j.devcel.2020.10.025
通讯作者	Liu, Yansheng(yansheng.liu@yale.edu)
英文摘要	To date, the effects of specific modification types and sites on protein lifetime have not been systematically illustrated. Here, we describe a proteomic method, DeltaSILAC, to quantitatively assess the impact of site-specific phosphorylation on the turnover of thousands of proteins in live cells. Based on the accurate and reproducible mass spectrometry-based method, a pulse labeling approach using stable isotope-labeled amino acids in cells (pSILAC), phosphoproteomics, and a unique peptide-level matching strategy, our DeltaSILAC profiling revealed a global, unexpected delaying effect of many phosphosites on protein turnover. We further found that phosphorylated sites accelerating protein turnover are functionally selected for cell fitness, enriched in Cyclin-dependent kinase substrates, and evolutionarily conserved, whereas the glutamic acids surrounding phosphosites significantly delay protein turnover. Our method represents a generalizable approach and provides a rich resource for prioritizing the effects of phosphorylation sites on protein lifetime in the context of cell signaling and disease biology.
资助项目	National Institute of General Medical Sciences (NIGMS) ; National Institutes of Health (NIH)[R01GM137031] ; Cancer Systems Biology@Yale ; Yale Cancer Center at Yale University ; Czech Academy of Sciences, Czech Republic[L200521953] ; Schram Stiftung[T0287/35359/2020] ; DFG[FO 1342/1-3]
WOS关键词	DATA-INDEPENDENT ACQUISITION ; CELL-CULTURE ; DYNAMICS ; QUANTIFICATION ; IDENTIFICATION ; PROTEOMICS ; STABILITY ; REVEALS ; PEPTIDE ; SILAC
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000607158400011
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296140]
专题	中国科学院上海药物研究所
通讯作者	Liu, Yansheng
作者单位	1.Yale Univ, Yale Canc Biol Inst, West Haven, CT 06516 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 201203, Peoples R China 3.DKFZ, German Canc Res Ctr, D-69120 Heidelberg, Germany 4.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Columbia Univ, Dept Syst Biol, New York, NY USA 6.Univ Med Ctr Gottingen, Dept Neuro & Sensory Physiol, D-37073 Gottingen, Germany 7.Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA 8.Czech Acad Sci, Dept Genome Integr, Inst Mol Genet, Prague, Czech Republic
推荐引用方式 GB/T 7714	Wu, Chongde,Ba, Qian,Lu, Dayun,et al. Global and Site-Specific Effect of Phosphorylation on Protein Turnover[J]. DEVELOPMENTAL CELL,2021,56(1):111-+.
APA	Wu, Chongde.,Ba, Qian.,Lu, Dayun.,Li, Wenxue.,Salovska, Barbora.,...&Liu, Yansheng.(2021).Global and Site-Specific Effect of Phosphorylation on Protein Turnover.DEVELOPMENTAL CELL,56(1),111-+.
MLA	Wu, Chongde,et al."Global and Site-Specific Effect of Phosphorylation on Protein Turnover".DEVELOPMENTAL CELL 56.1(2021):111-+.