EPIDERMAL INJURY STIMULATES PRENYLATION IN THE EPIDERMIS OF HAIRLESS MICE

Isoprenylation is the covalent attachment of isoprenyl groups, interme diates of the cholesterol biosynthesis pathway, to carboxy terminal cy steine residues of proteins, Numerous proteins are isoprenylated inclu ding small GTP binding proteins, trimeric G proteins, and nuclear lami ns, and these prenylated proteins regulate a variety of cell functions , including cell growth, cytokinesis, and differentiation. Here, we qu antitated protein prenylation and determined which proteins are prenyl ated in the epidermis of hairless mice by radiolabeling with H-3-meval onolactone following acute or chronic epidermal injury, In normal epid ermis, four major radiolabeled bands, with molecular weights of 17-26, 48, 54, and 68 kDa, were observed, The levels of each of these bands increased by 24-63 % 16 h following acute epidermal injury induced by topical acetone treatment or tape stripping, returning to normal by 24 h, On 2D gel electrophoresis, there were no major differences between the patterns of labeling following barrier disruption, Subacute epide rmal injury induced by either acetone or tape stripping twice a day fo r 7 days and chronic injury induced by feeding an essential fatty acid -deficient (EFAD) diet, also resulted in a significant increase in pro tein prenylation. As with acute injury, SDS-PAGE and 2D gel electropho resis did not reveal marked differences in the pattern of protein pren ylation. These results demonstrate that the prenylation of proteins in the epidermis is stimulated by injury, suggesting that one or more of these prenylated species may be important in epidermal proliferation or differentiation.