TXNIP interacts with hEcd to increase p53 stability and activity

Abstract

The p53 protein plays a central role in cell cycle arrest and apoptosis in response to diverse stress stimuli. Human ecdysoneless (hEcd) is known for its role in stabilizing the p53 protein level and increasing p53-mediated transcription. Here, we report that thioredoxin interacting protein (TXNIP), a member of the tumor suppressor family, interacts with hEcd and decreases MDM2-mediated p53 ubiquitination, leading to p53 stabilization and an increase in p53 activity. The ectopic overexpression of both TXNIP and Ecd increased actinomycin D-mediated cell death in MCF-7 cells, whereas knockdown of TXNIP and Ecd decreased cell death. These results show that TXNIP is a new regulator of the Ecd-MDM2-p53 loop.