S100 proteins interact with the transactivation domain and the C-terminus of 
p53. Further, S100B has been shown to interact with MDM2, a central negative 
regulator of p53. Here, we show that S100B bound directly to the folded 
N-terminal domain of MDM2 (residues 2-125) by size exclusion chromatography and 
surface plasmon resonance experiments. This interaction with MDM2 (2-125) is a 
general feature of S100 proteins; S100A1, S100A2, S100A4 and S100A6 also 
interact with MDM2 (2-125). These interactions with S100 proteins do not result 
in a ternary complex with MDM2 (2-125) and p53. Instead, we observe the ability 
of a subset of S100 proteins to disrupt the extent of MDM2-mediated p53 
ubiquitylation in vitro.