Regulation of human glucocorticoid receptor gene transcription by Sp1 and p53.
The human glucocorticoid receptor (hGR) gene has several GC boxes in the promoter 1C region. We studied the effects of Sp1 and p53 on promoter 1C in HepG2 and HEK293 cells using luciferase (Lu) reporter assay. The results showed that the first GC box upstream of the transcription site activated the hGR promoter and over-expression of Sp1 obviously enhanced the activity. A mutant Lu-hGR vector, whose first GC box was defective, lost promoter activity nearly completely. Further, over-expression of p53 strongly suppressed the stimulating effect of Sp1 on hGR promoter activity. We concluded that Sp1 activates the hGR gene promoter, at least in part, by acting on the first GC box in promoter 1C, while p53 suppresses the transactivation by Sp1. These phenomena, demonstrated in cultured cells, may be important for the expression of hGR in vivo.
Suehiro
Tadashi
T
Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan. suehirot@med.kochi-u.ac.jp
Kaneda
Tadafumi
T
Ikeda
Yukio
Y
Arii
Kaoru
K
Kumon
Yoshitaka
Y
Hashimoto
Kozo
K
D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D020862:GC Rich Sequence; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism* / Q000494:pharmacology; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism* / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D016329:Sp1 Transcription Factor; D016159:Tumor Suppressor Protein p53