S100 proteins interact with the N-terminal domain of MDM2.
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.
van Dieck
Jan
J
MRC Centre for Protein Engineering, Hills Road, Cambridge CB2 0QH, UK.
Lum
Jenifer K
JK
Teufel
Daniel P
DP
Fersht
Alan R
AR
D001665:Binding Sites; D019921:Biotinylation; D002850:Chromatography, Gel; D006801:Humans; D008027:Light; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry* / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism*; D012542:Scattering, Radiation; D020349:Surface Plasmon Resonance; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054875:Ubiquitination
D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2