Fig 7. A model for the role of MDM2-MDM4 heterodimers in regulation of p53 and cell cycle.

MDM2-MDM4 heterodimer mediated p53 ubiquitination and proteasomal degradation is essential for restricting p53 activity during embryonic development and for a rapid and robust p53 checkpoint response. Inhibition of p53 transactivation by MDM2-MDM4 heterodimers plays a marginal role in these processes. MDM2 E3 ligase activity is required for p53-independent cell cycle regulation via uncharacterized mechanisms involving Factor X degradation. Thick arrow, strong effect, thin arrow, marginal effect.