Self-association of calcium-binding protein S100A4 and metastasis


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:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > 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
Publication ISSN: 1083-351X
Last Modified: 16 Jan 2024 17:23
Date Deposited: 08 Sep 2010 11:08
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.jbc. ... ntent/285/2/914 (Publisher URL)
PURE Output Type: Article
Published Date: 2010-01-08
Authors: Ismail, Thamir M.
Zhang, Shu
Fernig, David G.
Gross, Stephane R. (ORCID Profile 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



Version: Published Version

| Preview

Export / Share Citation


Additional statistics for this record