PXD014737

PXD014737 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteome analysis reveals the importance of Greatwall-endosulfine pathway to regulate cell-cycle progression upon the rapamycin-induced autophagy
Description	Protein phosphorylation plays an important role in the process of autophagy. Autophagy is associated with cell cycle, which is controlled by the balance between the cyclin-dependent kinases and phosphatases activities. However, up to now, the signal transduction pathways that underlied rapamycin-induced autophagy and cell cycle have remained elusive. Here, we used stable isotope labeling of amino acids in cell culture and high-throughput quantitative mass spectrometry to perform a global proteome and phosphoproteome analysis of rapamycin-induced autophagy in vitro. By monitoring proteome and phosphoproteome alterations with rapamycin treatment, we detected downregulation of mTOR signaling pathway and confirmed the occurrence of autophagy. Additionally, spliceosome and nuclear pore complexes were enriched to be regulated, which further validated autophagy as a stress response itself. More importantly, we discovered that mTORC1 could control cell cycle progression though Greatwall-endosulfine-PP2A pathway in HeLa cells. Firstly, we found the elevated profile of cell cycle-related substrates and determined the enrichment of CDK1, MAPK1 and MAPK3 kinases, which implied the activation of these kinases. Secondly, Pathway interrogation using kinase inhibitor treatment confirmed the effect of mTOR inhibition on CDK1 activity and cell cycle progression. Thirdly, we discovered that Greatwall-endosulfine complex was required to mediate mTOR-mediated cell-cycle progression. In conclusion, we presented a high-confidence map of phosphoproteomic of autophagy and unveiled the Greatwall-endosulfine pathway to regulate cell-cycle progression in the rapamycin-induced autophagy.
HostingRepository	PRIDE
AnnounceDate	2021-04-06
AnnouncementXML	Submission_2021-04-05_23:10:26.609.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	luqi jin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-24 08:01:56	ID requested
⏵ 1	2021-04-05 23:10:27	announced

Jin L, Chen Y, Yan C, Guo X, Jiang T, Guli A, Song X, Wan Q, Shu Q, Ding S, Phosphoproteome Profiling Revealed the Importance of mTOR Inhibition on CDK1 Activation to Further Regulate Cell Cycle Progression. J Proteome Res, 20(5):2329-2339(2021) [pubmed]

submitter keyword: autophagy

phosphoproteome

rapamycin

cell cycle

CDK1

Shiping Ding
contact affiliation	Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
contact email	dingshiping@zju.edu.cn
lab head
luqi jin
contact affiliation	zhejiang university
contact email	21818568@zju.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014737
     1. Label: PRIDE project
     2. Name: Phosphoproteome analysis reveals the importance of Greatwall-endosulfine pathway to regulate cell-cycle progression upon the rapamycin-induced autophagy