Comparative proteomic analysis of cisplatin-and oxaliplatin-induced phosphorylation in proteins bound to Pt-DNA adducts
作者单位:State Key Laboratory of Coordination ChemistryCoordination Chemistry InstituteSchool of Chemistry and Chemical EngineeringNanjing University National Center for Protein Sciences BeijingState Key Laboratory of ProteomicsBeijing Proteome Research CenterBeijing Institute of Lifeomics Department of Biomedical EngineeringCollege of Engineering and Applied SciencesNanjing University
会议名称:《第十一届全国化学生物学学术会议》
会议日期:2019年
学科分类:1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学]
关 键 词:cisplatin oxaliplatin Pt-DNA probe phosphoproteome DNA damage response
摘 要:Cisplatin and oxaliplatin are widely used chemotherapeutic agents with different anti-tumor spectra.[1] Cisplatin is believed to covalently bind DNA nucleobases, and such Pt-DNA adducts cause replication and transcription blockage and ultimately leads to apoptosis. Oxaliplatin has been demonstrated to trigger not only DNA damage response but also ribosome biogenesis stress.[2] However, it is not entirely clear how cisplatin and oxaliplatin differs in their mechanisms of inducing cancer cell death. In order to understand the differences in protein phosphorylation patterns caused by cisplatin and oxaliplatin, a label-free proteomic strategy was employed to investigate such damage response processes using Pt-DNA probes. Proteins involved in recognition of specific Pt-DNA lesions were pulled down. Following phosphorylation enrichment and LC-MS analysis, phosphoproteome comparison of colon cancer cells treated with different platinum drugs yielded differentially phosphorylated protein datasets with respect to untreated cells. These identification results clearly show different protein phosphorylation patterns and reflect distinctive mechanisms of actions between cisplatin and oxaliplatin. Such protein phosphorylation patterns may provide novel therapeutic targets and diagnostic biomarkers for the future development of platinum-based drugs.