Regulation of a novel immediate early response gene, IEX-1, in keratinocytes by 1α,25-dihydroxyvitamin D3

1 alpha,25-Dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] regulates cellular growth and differentiation. We show that in keratinocytes, 1 alpha,25(OH)(2)D-3 reduces concentrations of the messenger RNA of IEX-1, the product of which blocks Fas- or tumor necrosis factor type a-induced apoptosis in various cells. In sub confluent keratinocyte cultures, the addition of 1 alpha,25(OH)(2)D-3, in amounts that induce growth arrest, reduces IEX-1 mRNA concentrations. In confluent cells, 1 alpha,25(OH)(2)D-3 initially reduces and then increases IEX-1 mRNA concentrations. IEX-1 protein is localized in the nucleus and perinuclear region of keratinocytes, In sub-confluent cells, 1 alpha,25(OH)(2)D-3 translocates IEX-1 protein from the nucleus to the perinuclear region and cytoplasm. Since IEX-1 has recently been shown to regulate cell survival and number, we suggest that IEX-1 may play a role in keratinocyte growth and differentiation and that 1 alpha,25(OH)(2)D-3 may reduce keratinocyte growth via a reduction in IEX-1 mRNA and a change in the intracellular distribution of IEX-1 protein. (C) 1998 Academic Press.