ABSTRACT
The mammalian epidermis forms a vital barrier between an organism and its environment. It is continuously replaced through the proliferation of basal keratinocytes, which migrate upwards and differentiate into spinous and granular cells, eventually forming the stratum corneum or anuclear squames that constitute the epidermal barrier. During the process of terminal differentiation, epidermal keratinocytes produce a large number of proteins that function either as structural components of the stratum corneum or are involved in its synthesis or assembly. One of the largest families of epidermally expressed genes is the S100 Ca2þ-binding proteins, which function as calcium-dependent sensors, modulating a diverse array of intracellular and extracellular processes. The S100 protein family can be regarded as a superfamily consisting of two related groups, namely the low molecular weight canonical S100 proteins of 100 amino acids and the high molecular weight fused S100 family, which contains an N-terminal S100 domain, ‘‘fused’’ to other sequences. The S100 domain consists of two EF-hands with flanking a-helices that are critical for calcium binding and protein-protein interactions (Fig. 1). The canonical S100 proteins form homodimers, and heterodimers with other S100 proteins. Upon calcium binding, these dimers associate with specific target proteins, which regulate their activity and/or subcellular distribution (1,2). This review will focus on the fused S100 family, with only limited discussion of the canonical S100 family, which have been the subject of several recent reviews (1-3).
