Regulation of a novel immediate early response gene, IEX-1, in keratinocytes by 1alpha,25-dihydroxyvitamin D3.
1alpha,25-Dihydroxyvitamin D3 [1alpha,25(OH)2D3] regulates cellular growth and differentiation. We show that in keratinocytes, 1alpha, 25(OH)2D3 reduces concentrations of the messenger RNA of IEX-1, the product of which blocks Fas- or tumor necrosis factor type alpha-induced apoptosis in various cells. In sub-confluent keratinocyte cultures, the addition of 1alpha,25(OH)2D3, in amounts that induce growth arrest, reduces IEX-1 mRNA concentrations. In confluent cells, 1alpha,25(OH)2D3 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, 1alpha,25(OH)2D3 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 1alpha,25(OH)2D3 may reduce keratinocyte growth via a reduction in IEX-1 mRNA and a change in the intracellular distribution of IEX-1 protein.
Kobayashi
T
T
Departments of Medicine, Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
Pittelkow
M R
MR
Warner
G M
GM
Squillace
K A
KA
Kumar
R
R
D051017:Apoptosis Regulatory Proteins; D001692:Biological Transport; D002117:Calcitriol / Q000494:pharmacology*; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D002117:Calcitriol