Fig. 1.

MDMX acidic domain regulates MDMX and p53 through intra- and intermolecular interactions. (A) A model of p53 inhibition by MDMX. The central acidic domain (AD) of MDMX engages in intramolecular interactions with the p53 binding domain (p53BD) and RING domains in the absence of p53. CK1α binding disrupts intramolecular interactions of AD with p53BD, increasing the apparent affinity of the MDMX N terminus for p53. Following formation of the initial MDMX–p53 complex, the AD also establishes interaction with the p53 core domain, stabilizing the complex and blocking p53 binding to DNA. (B) Partial sequence of the MDMX AD showing the conserved WW motif important for autoinhibition and the substitution mutations introduced into the mouse germline.