Distinct functions of wild-type and R273H mutant Δ133p53α differentially regulate glioblastoma aggressiveness and therapy-induced senescence.

ABSTRACT: Mutations effects on p53 isoforms' activities remain largely unknown, although they are mutated in 92% of TP53 mutant cancers. Therefore, exploring the effect of mutations on p53 isoforms activities is a critical, albeit unexplored area in the p53 field. In this article, we report for the first time a mutant Δ133p53α-specific pathway which increases IL4I1 and IDO1 expression and activates AHR, a tumor-promoting mechanism. Accordingly, mutant Δ133p53α R273H increases glioblastoma cancer cells proliferation and invasion while the WT does not. Furthermore, while WT Δ133p53α reduces apoptosis to promote DNA repair, the mutant also reduces apoptosis but fails to maintain genomic stability.Furthermore, both WT and mutant Δ133p53α reduce cellular senescence in a senescence inducer-dependen

SUBMITTER: Harris C 

PROVIDER: S-EPMC10659536 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature