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- W2165961971 abstract "The physiological effects of glucose-dependent insulinotropic polypeptide (GIP) are mediated through specific receptors expressed on target cells. Because aberrant GIP receptor ( GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. We previously demonstrated that sequences between −1 and −100 of the GIPR gene were sufficient to direct transcription in a rat insulinoma cell line (RIN38). In the present study, we compared the 5′-flanking regions of the rat and human GIPR gene and demonstrated 88% identity within the first 92 bp. Subsequent serial deletion analyses showed that the region between −85 and −40 is essential for maximal promoter activity. Within this region, we identified three putative Sp1 binding motifs, located at positions −77, −60, and −50, that can specifically bind both Sp1 and Sp3. Whereas mutation of the Sp1 sites at −50 and −60 led to 36 and 40% reduction in promoter activity, respectively, mutation of the Sp1 motif at −70 did not affect promoter activity. Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between −100 and −40. Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. These results indicate that cell-specific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter." @default.
- W2165961971 created "2016-06-24" @default.
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- W2165961971 date "2006-06-01" @default.
- W2165961971 modified "2023-09-26" @default.
- W2165961971 title "Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene" @default.
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- W2165961971 doi "https://doi.org/10.1152/ajpendo.00535.2005" @default.
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