Divergent regulation of the growth-promoting gene IEX-1 by the p53 tumor suppressor and Sp1.
IEX-1, a recently discovered early response gene, regulates cell growth and apoptosis. IEX-1 gene expression is regulated by a variety of factors such as x-irradiation, ultraviolet radiation, steroids, growth factors, and inflammatory stimuli. By systematic examination of the IEX-1 promoter, we show that IEX-1 gene expression is controlled by multiple conserved gene regulatory elements and that IEX-1 is a downstream target of the p53 tumor suppressor and Sp1. In addition, p300, Sox, nuclear factor-kappaB, and AP4 appear to be modulators of IEX-1 gene expression to a lesser degree. We found that there is at least one Sp1 element that functions as an activator and contributes to high basal transcriptional levels of the IEX-1 gene. We demonstrate the presence of a p53 response element that represses IEX-1 promoter activity in HaCaT keratinocytes, indicating that Sp1 and p53 have opposite effects on IEX-1 gene expression. We conclude that IEX-1 expression in cells is regulated by the p53 tumor suppressor and Sp1, thus providing a direct mechanism for control of cell proliferation.
Im
Hee-Jeong
HJ
Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Pittelkow
Mark R
MR
Kumar
Rajiv
R
D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins; D016297:Mutagenesis, Site-Directed; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C099815:IER3 protein, human; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53