Transglutaminases(TGases) catalyze the formation of an isodipeptide cross-link between the ε-NH2 side chain of a protein-bound lysine residue and the γ-amide side chain of a protein-bound glutamine residue, thereby making an insoluble
macromolecular
aggregate that is used for a variety of cellular functions. To date, there are six known TGase enzymes encoded by human genome, and three of them are active in the epidermis and its appendages. These include the TGasel (TGase K) which can
function
mainly as a membrane-associated, proteolytically activated processed form; the soluble, tissue TGase2(TGase C); and the soluble TGase3 (TGase E). which also requires proteolytic activation. The role of these enzymes in the fate of differentiating
epidermis and hair follicle cells is not yet clear. TGase2 has been implicated in apoptosis, cell adhesion, and signal transduction. TGase1 and 3 are thought to be required to form a specialized structure term the cornified cell envelope which
provides
vital barrier functions. The involvement of TGases in cell envelope formation is supported by two types of observations. First, many analyses demonstrated ε(γ-glutamyl) lysine cross-link to be present in the cell envelope. Second, many in vitro
cross-linking studies have shown that the cell envelope proteins or model peptides derived from them are efficiently used as substrates by TGases. More interestingly, mutations in the TGM1 gene were shown to be the cause of lamellar ichthyosis
characterized by large, brown or black, plate-like scale in a generalized distribution. In this review, we will outline the current understanding about three TGases which are active in the epidermis, and discuss their roles in the fate of
differentiating epidermal cells.
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