Gain-of-function p53 activates multiple signaling pathways to induce oncogenicity in lung cancer cells.

ABSTRACT: Gain-of-function (GOF) mutants of p53 upregulate genes implicated in cell proliferation and oncogenesis. Here, we report that GOF p53 induces tumorigenicity through simultaneous activation of key oncogenic pathways including those controlling putative tumor-initiating cell functions. We determined that in cells expressing p53-R273H, GOF p53 simultaneously upregulates genes from multiple signaling pathways by recognizing promoters containing distinct transcription factor (TF) binding sites. Our analytical data support a model in which GOF p53 complexes with two TFs on the promoter-a mediator protein, Med17, and a histone acetyl transferase, activating histone acetylation-and enhances gene expression to signal cell proliferation and oncogenesis. Thus, therapeutic inhibition of one GOF p53-in

SUBMITTER: Vaughan CA 

PROVIDER: S-EPMC5467493 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature