Transcriptional regulation of the gene encoding the 78-kD glucose-regulated protein GRP78 in mouse sertoli cells: binding of specific factor(s) to the GRP78 promoter.
We investigate the mechanism by which expression of the GRP78 gene is regulated using a mouse Sertoli cell line as an experimental system. We identify testosterone as a new inducer of the GRP78 gene in these cells. Furthermore, we show that despite their unusually low basal level of GRP78 mRNA, Sertoli cells retain the capacity to induce the GRP78 gene to high levels when challenged with the calcium ionophore A23187. Cellular factors present in whole-cell extracts isolated from Sertoli cells under noninduced and A23187-induced conditions bind specifically to a region of the GRP78 promoter previously identified as essential for maintenance of basal level expression and A23187 induction. We detect no difference in the binding of protein factors in the extracts prepared from noninduced versus induced cells. On the basis of this data, we propose models by which induction of the GRP78 gene may occur.
Department of Biochemistry, Norris Cancer Research Institute, University of Southern California School of Medicine, Los Angeles 90033.
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D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007700:Kinetics; D008297:Male; D051379:Mice; D018832:Molecular Chaperones; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012708:Sertoli Cells; D013739:Testosterone / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D012333:RNA, Messenger; D014157:Transcription Factors; D013739:Testosterone; D004247:DNA