Binding to intracellular targets of the metastasis-inducing protein, S100A4 (p9Ka).
Experimentally elevated levels of S100A4 induce a metastatic phenotype in benign mammary tumour cells in vivo. In humans, the presence of S100A4 in breast cancer cells correlates strongly with reduced patient survival. Potential interacting binding partners for S100A4 have now been examined using an optical biosensor. There was significant interaction of S100A4 with non-muscle myosin and p53, but not with actin, tropomyosin or tubulin. The results suggest that myosin and p53 are likely to be intracellular targets of S100A4. S100A4 had a greater affinity for wild-type or mutant arg-175-his p53 than for non-muscle myosin. The results suggest that S100A4 might induce metastasis by influencing the function of p53 as well as through its interaction with myosin and that any mechanism is independent of the mutational status of p53.
Chen
H
H
Molecular Medicine Research Group, University of Liverpool, Liverpool, L69 7ZB, United Kingdom.
Fernig
D G
DG
Rudland
P S
PS
Sparks
A
A
Wilkinson
M C
MC
Barraclough
R
R
D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051379:Mice; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D009362:Neoplasm Metastasis; D010641:Phenotype; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors; D014335:Tropomyosin / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018076:DNA, Complementary; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C499412:S100a4 protein, rat; D014335:Tropomyosin; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; C077591:S100A4 protein, human; D009218:Myosins