Proteins of the S100 family regulate the oligomerization of p53 tumor suppressor.
S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome. S100A4 is correlated with the development of metastasis. Both proteins bind to p53 tumor suppressor. We found that both S100B and S100A4 bind to the tetramerization domain of p53 (residues 325-355) only when exposed in lower oligomerization states and so they disrupt the tetramerization of p53. In addition, S100B binds to the negative regulatory and nuclear localization domains, which results in a very tight binding to p53 protein sequences that exposed the tetramerization domain in their C terminus. Because the trafficking of p53 depends on its oligomerization state, we suggest that S100B and S100A4 could regulate the subcellular localization of p53. But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control.
Fernandez-Fernandez
Maria Rosario
MR
Centre for Protein Engineering, Medical Research Council, Cambridge CB2 2QH, UK.
Veprintsev
Dmitry B
DB
Fersht
Alan R
AR
D000595:Amino Acid Sequence; D019793:Fluorescein; D005454:Fluorescence Polarization; D040461:Gene Components; D006801:Humans; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors; D011108:Polymers / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D009414:Nerve Growth Factors; D011108:Polymers; D064568:S100 Calcium Binding Protein beta Subunit; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C579160:S100B protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C077591:S100A4 protein, human; D019793:Fluorescein