Work

MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis

Year: 2018

Type: article

Abstract: Significance MDMX is an important regulator of p53 during embryonic development and malignant transformation. Using a combination of mouse knockin model, cell culture, and biochemical analysis, we demonstrate that the MDMX acidic domain interacts with the p53 DNA-binding domain and inhibits p53 DNA binding in the test tube and in tissues. This interaction is important for regulating p53 transcriptional activity and tumor suppressor function under physiological conditions. Furthermore, the results suggest that the MDMX acidic domain has p53-independent function that inhibits the progression of Myc-mediated lymphomas. The study provides physiological evidence on the mechanism of p53 regulation by MDMX, and identifies the structural basis for novel MDMX activities that warrants future investigation.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1719090115