Efficient p53 activation and apoptosis induction of MDM2/MDMX inhibitory protein, a recombinant cell-permeable fusion protein, in p53- breast cancer cells.

e13524 Background: P53 is the most important tumor suppressor and it plays a key role in protection against malignant transformation. MDM2 and MDMX are important regulators of the transcriptional activity and stability of p53 by binding to its NH2 terminus. Recent studies suggest that inhibition of both MDM2 and MDMX is necessary for robust activation of p53 in certain tumor cells. The p53 activation effect of MDM2/MDMX inhibition is more when combined than MDM2 inhibition or MDMX inhibition alone. So searching for a new MDM2/MDMX inhibitor is a promising approach for cancer therapy. Methods: A cell-permeable MDM2/MDMX inhibitory fusion protein, containing TAT peptide for transduction across membranes and the scaffold protein (thioredoxin) displaying the MDM2/MDMX inhibitory peptide pDI, was constructed and expressed by molecular cloning and prokaryotic expression technology. ELISA and co-immunoprecipitation were used to evaluate the feasibility and biological effects of simultaneously disrupting p53 bind...