A novel immediate early response gene, IEX-1, is induced by ultraviolet radiation in human keratinocytes.
Skin cancer is the most common human malignancy and is strongly associated with exposure to ultraviolet radiation (UVR). Several mechanisms including an increase in immediate early gene activation have been postulated to be involved in UVR-mediated carcinogenesis. We show that in a dose-dependent manner, UVR induces the expression of messenger RNA of a novel immediate early response gene, IEX-1, in human keratinocytes. Human keratinocytes and mouse fibroblasts transfected with an expression plasmid for IEX-1 grow at a faster rate than keratinocytes transfected with a similar plasmid that does not contain the IEX-1 sequence. IEX-1 protein is localized predominantly in the nucleus of keratinocytes by fluorescent antibody methods and by examination of the location of a green fluorescence IEX-1 fusion protein. Epidermal growth factor (EGF), a major mitogen of keratinocytes, and a tumor-promoting phorbol ester increase IEX-1 mRNA expression. IEX-1 may play a role in keratinocyte proliferation especially following UVR.
Kumar
R
R
Nephrology Research Unit, Mayo Clinic and Foundation, Rochester, Minnesota, 55905, USA.
Kobayashi
T
T
Warner
G M
GM
Wu
Y
Y
Salisbury
J L
JL
Lingle
W
W
Pittelkow
M R
MR
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002461:Cell Line, Transformed; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects*; D049452:Green Fluorescent Proteins; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D008164:Luminescent Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D010957:Plasmids; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014466:Ultraviolet Rays
D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor