MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail.

ABSTRACT:

Background

MDM2 is an E3 ubiquitin ligase that is able to ubiquitinate p53, targeting it for proteasomal degradation. Its homologue MDMX does not have innate E3 activity, but is able to dimerize with MDM2. Although mouse models have demonstrated both MDM2 and MDMX are individually essential for p53 regulation, the significance of MDM2-MDMX heterodimerization is only partially understood and sometimes controversial. MDM2^C462A mice, where the C462A mutation abolishes MDM2 E3 ligase activity as well as its ability to dimerize with MDMX, die during embryogenesis. In contrast, the MDM2^Y487A mice, where the Y487A mutation at MDM2 C-terminus significantly reduces its E3 ligase activity without disrupting MDM2-MDMX binding, survive normally even though p53 is expresse

SUBMITTER: Sanford JD 

PROVIDER: S-EPMC8459461 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature