Proteomics

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An integrative multi-omics approach uncovers the regulatory role of Cdk7 and Cdk4 in autophagy induced by silica nanoparticles


ABSTRACT: 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.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Xue Yu  

PROVIDER: PXD012196 | iProX | Sun Dec 01 00:00:00 GMT 2019

REPOSITORIES: iProX

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An integrative multi-omics approach uncovers the regulatory role of CDK7 and CDK4 in autophagy activation induced by silica nanoparticles.

Ruan Chen C   Wang Chenwei C   Gong Xuanqing X   Zhang Ying Y   Deng Wankun W   Zhou Jiaqi J   Huang Dengtong D   Wang Zining Z   Zhang Qiong Q   Guo Anyuan A   Lu Jiahong J   Gao Jinhao J   Peng Di D   Xue Yu Y  

Autophagy 20200523 6


Dysfunction of macroautophagy/autophagy has been postulated as a major cellular toxicological response to nanomaterials. It has been reported that excessive autophagy activation, induced by silica nanoparticles (SiNPs), contributes to autophagy dysfunction, whereas little is known how SiNPs trigger autophagy activation. Here, we treated normal rat kidney (NRK) cells using 3 different sizes of SiNPs (16, 29, and 51 nm) and observed that 16-nm SiNPs, with a final concentration of 60 μg/mL, dramati  ...[more]

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