Work

Identification of a cis-Regulatory Element for Δ12-Prostaglandin J2-induced Expression of the Rat Heme Oxygenase Gene

Year: 1995

Type: article

Abstract: We recently reported that delta 12-prostaglandin (PG) J2 caused various cells to synthesize heme oxygenase, HO-1 (Koizumi, T., Negishi, M., and Ichikawa, A. (1992) Prostaglandins 43, 121-131). Here we examined the molecular mechanism underlying the delta 12-PGJ2-induced HO-1 synthesis. delta 12-PGJ2 markedly stimulated the promoter activity of the 5'-flanking region of the rat HO-1 gene from -810 to +101 in rat basophilic leukemia cells. From functional analysis of various deletion mutant genes we found that the delta 12-PGJ2-responsive element was localized in a region from -690 to -660, containing an E-box motif, which was essential for the delta 12-PGJ2-stimulated promoter activity. When the region containing the delta 12-PGJ2-responsive element was combined with a heterologous promoter, SV40 promoter, in the sense and antisense direction, the element showed an enhancer activity in response to delta 12-PGJ2. Gel mobility shift assays demonstrated that delta 12-PGJ2 specifically stimulated the binding of two nuclear proteins to the E-box motif of this region. These results indicate that delta 12-PGJ2 induces the expression of the rat HO-1 gene through nuclear protein binding to a specific element having an E-box motif.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.270.37.21779

Authors: Tomonobu Koizumi, Noriko Odani, Tohko Okuyama, Atsushi Ichikawa, Manabu Negishi

Institution: Kyoto University

Language: English

Topic: Heme Oxygenase-1 and Carbon Monoxide

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430