ReviewA review of the S100 proteins in cancer
Introduction
The S100 proteins are a multi-gene calcium-binding family comprising 20 known human members each coded by a separate gene. At least 16 of these genes cluster to chromosome 1q21, known as the epidermal differentiation complex1, 2 (Table 1). The S100 proteins are small, acidic proteins of 10–12 kDa, found exclusively in vertebrates.3 The first member was identified in 1965 by Moore who christened a subcellular fraction from bovine brain “S100” because the constituents were soluble in 100% saturated ammonium sulphate at neutral pH.4, 5 Since then expression of S100 proteins has been demonstrated in a diverse spectrum of tissues. This paper summarizes the expression pattern of different members of the family in various solid tumours and discusses how detection may be useful for diagnosis, monitoring and as possible therapeutic targets.
The nomenclature of these proteins is very complex; each individual protein is known by several names, which can make processing the literature challenging. This has recently been simplified and the current nomenclature is summarised in Table 1.
Section snippets
Structure
The S100 proteins belong to the Ca2+- binding EF-hand motif superfamily and have the ability to form homodimers, heterodimers and oligomers. EF-hand motifs are calcium-binding motifs composed of two helixes (E and F) joined by a loop and it is the loop region that binds calcium. The S100 proteins have two distinct EF-hands, one common to all EF-hand proteins on the C-terminal portion and one specific to this family located at the N-terminus. Subsequent to the C-terminal EF-hand region is a
Functions of S100 proteins
It is well documented that S100 proteins have a broad range of intracellular and extracellular functions. Intracellular functions include regulation of protein phosphorylation and enzyme activity, calcium homeostasis, regulation of cytoskeletal components and regulation of transcriptional factors.
A number of S100 proteins interact with p53,3, 7, 8 however they exert different effects on p53 activity. Both S100A4 and S100B are thought to inhibit p53 phosphorylation leading to inhibition of its
Conclusion
There has been growing interest in the S100 protein family and their relationship with different cancers. While the precise role of S100 proteins in the development and promotion of cancer remains unclear, it is evident that the S100 proteins have a variety of intracellular and extracellular roles, and that disruption to any one of these functions may contribute to carcinogenesis. Precise mechanisms are still to be established, but there is evidence that these proteins play a major role in
Acknowledgements
We would like to thank Dr. R. Reynolds for all his advice.
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