Table 2.

Other cellular factors that interact with Mdm2 or Mdmx.

Binding cofactor	Mdm2	Mdmx
Arf	Arf binds to and sequesters Mdm2 in the nucleolus, which leads to increased p53 levels and activity [81].	Mdmx can prevent Arf-induced p53 activation and growth arrest. However, whether Mdmx binds to Arf directly remains controversial [83,86, 89].
	Arf also promotes sumoylation of Mdm2, which might contribute to the ability of Arf to relocalize Mdm2 to the nucleolus [120].
p300	p300 binds to both Mdm2 and p53 to form a ternary complex and has been shown to enhance Mdm2-mediated ubiquitination and degradation of p53 [87].	Mdmx can inhibit p53 acetylation induced by endogenous and ectopically expressed p300 [84].
	Structural studies indicate that phosphorylation of the p53 transactivation domain increases the affinity of p53 for p300 and decreases binding to Mdm2, which may contribute to the stabilization and activation of p53 [90].	Mdmx may also exert p53-independent functions, as it can compete with Smad3/4 transcription factors for binding to p300 [85].
Ribosomal proteins	Nucleolar stress induced by serum starvation or non-genotoxic doses of Actinomycin D and 5-Fluorouracil promotes the binding of ribosomal proteins RPL5, -11, -23 and RPS-7 to Mdm2. This blocks Mdm2 E3 ligase function and increases p53 activity. Conversely, Mdm2 ubiquitylates and degrades RPL-26, leading to decreased p53 mRNA translation [82].	In contrast to Mdm2, Mdmx is not reported to bind directly to any ribosomal proteins. Rather, ribosomal stress can induce Mdm2-dependent Mdmx degradation in the absence of DNA damage, and overexpression of Mdmx can protect against agents that induce ribosomal stress [88].