摘要
Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways,it is still unclear how certain drugs influence these P53 signaling netw orks.Here,we used a comprehensive singlecell multiomics view of the effects of ginsenosides on cancer cells.Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely as sociated with P53 protein.A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins,and proteomemetabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism,amino acid metabolism and"Warburg effect".The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides.Furthermore,by applying affinity mass spectrometry(MS)screening and surface plasmon resonance fragment library screening,we confirmed that 20(S)-protopanaxatriol directly targeted adj acent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions,which further induced a series of omics changes.
基金
supported by International Cooperation and Exchange of the National Natural Science Foundation of China(No.81761168039)
Macao Science and TechnologyDevelopment 345 Fund(No.015/2017/AFJ,China)
National Key Research and Development Program of China(Nos.2018YFC1704800 and 2018YFC1704805)
作者简介
Corresponding authors:Yuanyuan Hou,E-mail address:houyy@nankai.edu.cn;Corresponding authors:Zhihong Jiang,E-mail address:zhjiang@must.edu.mo;Corresponding authors:Gang Bai E-mail address:gangbai@nankai.edu.cn
