PXD012196

PXD012196 is an original dataset announced via ProteomeXchange.

Title	An integrative multi-omics approach uncovers the regulatory role of Cdk7 and Cdk4 in autophagy induced by silica nanoparticles
Description	The abnormal induction of macroautophagy/autophagy, a highly conserved lysosome-based degradation pathway, has been postulated as a major toxicity of nanomaterials, whereas little is known on the exact molecular mechanisms. Here, we treated mammalian cells with 16 nm silica nanoparticles (SiNPs), conducted a transcriptomic, proteomic and phosphoproteomic profiling during autophagy, and detected up to 7208 (25.09%) genes potentially regulated in at least one level. To identify key regulators, we developed a new algorithm of computational prediction of master protein kinases (cMAK) to integrate the multi-omics data. Using cMAK, we predicted 21 candidates and validated a Cdk7-Cdk4 cascade to be functionally important, while the silence or inhibition of Cdk4 or Cdk7 significantly attenuated the autophagic induction and greatly diminished autophagosome formation. Our studies not only established a powerful method for predicting potentially regulatory kinases from the multi-omics data, but also revealed a novel mechanism of SiNPs-triggered autophagy through activating the Cdk7-Cdk4 cascade.
HostingRepository	iProX
AnnounceDate	2019-12-01
AnnouncementXML	Submission_2020-09-03_21:10:42.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chenwei Wang
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-28 18:19:53	ID requested
1	2019-12-01 20:49:48	announced
⏵ 2	2020-09-03 21:10:43	announced	2020-09-04: Update publication information

Ruan C, Wang C, Gong X, Zhang Y, Deng W, Zhou J, Huang D, Wang Z, Zhang Q, Guo A, Lu J, Gao J, Peng D, Xue Y, An integrative multi-omics approach uncovers the regulatory role of CDK7 and CDK4 in autophagy activation induced by silica nanoparticles. Autophagy, 17(6):1426-1447(2021) [pubmed]

submitter keyword: autophagy, silica nanoparticles, protein kinase, phosphoproteomics, Cdk4, Cdk7

Xue Yu
contact affiliation	Huazhong University of Science and Technology
contact email	xueyu@hust.edu.cn
lab head
Chenwei Wang
contact affiliation	Huazhong University of Science and Technology
contact email	reviewerfly2018@gmail.com
dataset submitter

iProX dataset URI