Global tumor protein p53/p63 interactome: making a case for cisplatin chemoresistance.

摘要: Cisplatin chemoresistance is a clinical problem that leads to treatment failure in various human epithelial cancers. Members of tumor protein (TP) p53 family play critical roles the multiple molecular mechanisms underlying cells. However, in-depth cellular response cisplatin-induced cell death are still under thorough investigation. We previously showed squamous carcinoma (SCC) cells exposed cisplatin display an ATM-dependent phosphorylation ΔNp63α, leading specific function phosphorylated (p)-ΔNp63α transcription factor cisplatin-sensitive further found SCC expressing non-p-ΔNp63α-S385G became cisplatin-resistant. Using quantitative mass-spectrometry complexes labeled with isobaric tags, we TP53 and ΔNp63α involved numerous protein-protein interactions, which likely be implicated exposure. p-ΔNp63α binds splicing complex, repression mRNA activation ACIN1-mediated pathway. In contrast p-ΔNp63α, non-p-ΔNp63α fails bind members thereby RNA reduction Overall, our studies provide integrated proteomic platform making case for role p53/p63 interactome chemoresistance.