Transcriptional repression of IKKβ by p53 in arsenite-induced GADD45α accumulation and apoptosis.

ABSTRACT: Our previous studies revealed that GADD45α is a liable protein, which undergoes MDM2-dependent constitutive ubiquitination and degradation in resting HepG2 hepatoma cells. Arsenite exposure induces ribosomal stress responses mediated by the ribosomal protein S7, which can block MDM2 activity and result in GADD45α accumulation and cell apoptosis. In the present study, we found that one of the catalytic subunits of IκB kinase (IKK), IKKβ, exerted a novel IKKα- and NF-κB-independent function in stabilizing MDM2 and therefore contributed to ubiquitination-dependent degradation of GADD45α in resting HepG2 cells. Arsenite stimulation induced transactivation of p53, which formed a complex with its downstream target, Ets-1, and then synergistically repressed IKKβ transcription, reduced MDM2 stabil

SUBMITTER: Hu Y 

PROVIDER: S-EPMC6355650 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature