Self-association of calcium-binding protein S100A4 and metastasis

Ismail, Thamir M., Zhang, Shu, Fernig, David G., Gross, Stephane R., Martin-Fernandez., Mrisa L., See, Violaine, Tozawa, Kaeko, Tynan, Christopher J., Wang, Guozheng, Wilkinson, Mark C., Rudland, Philip S. and Barraclough, Roger (2010). Self-association of calcium-binding protein S100A4 and metastasis. Journal of Biological Chemistry, 285 (2), pp. 914-922.

Abstract

Elevated levels of the calcium-binding protein S100A4 promote metastasis and in carcinoma cells are associated with reduced survival of cancer patients. S100A4 interacts with target proteins that affect a number of activities associated with metastatic cells. However, it is not known how many of these interactions are required for S100A4-promoted metastasis, thus hampering the design of specific inhibitors of S100A4-induced metastasis. Intracellular S100A4 exists as a homodimer through previously identified, well conserved, predominantly hydrophobic key contacts between the subunits. Here it is shown that mutating just one key residue, phenylalanine 72, to alanine is sufficient to reduce the metastasis-promoting activity of S100A4 to 50% that of the wild type protein, and just 2 or 3 specific mutations reduces the metastasis-promoting activity of S100A4 to less than 20% that of the wild type protein. These mutations inhibit the self-association of S100A4 in vivo and reduce markedly the affinity of S100A4 for at least two of its protein targets, a recombinant fragment of non-muscle myosin heavy chain isoform A, and p53. Inhibition of the self-association of S100 proteins might be a novel means of inhibiting their metastasis-promoting activities.

Publication DOI: https://doi.org/10.1074/jbc.M109.010892
Divisions: Life & Health Sciences > Biosciences
Life & Health Sciences
Life & Health Sciences > Cellular and Molecular Biomedicine
Additional Information: © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Uncontrolled Keywords: calcium-binding protein,S100A4,metastasis,carcinoma cells,survival,cancer patients,target proteins,metastatic cells,intracellular S100A4,residue,phenylalanine 72,Biochemistry,Cell Biology,Molecular Biology
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... ntent/285/2/914 (Publisher URL)
Published Date: 2010-01-08
Authors: Ismail, Thamir M.
Zhang, Shu
Fernig, David G.
Gross, Stephane R. ( 0000-0002-0867-8866)
Martin-Fernandez., Mrisa L.
See, Violaine
Tozawa, Kaeko
Tynan, Christopher J.
Wang, Guozheng
Wilkinson, Mark C.
Rudland, Philip S.
Barraclough, Roger

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