GLUT1 glucose transporter gene transcription is repressed by Sp3. Evidence for a regulatory role of Sp3 during myogenesis

GLUT1 glucose transporters are highly expressed in proliferating and transformed cells as well as in tissues during fetal life. However, the mechanisms that regulate GLUT1 gene expression remain largely unknown. Here, we demonstrate that Sp3 proteins bind to the GLUT1 proximal promoter gene and inhibit transcriptional activity in muscle and non-muscle cells. Two different Sp3 translational products (110 and 74 kDa) derived from differential translational initiation were detected in nuclear extracts from myoblast cells, and both Sp3 protein species inhibited GLUT1 gene transcriptional activity. The inhibitory effect of Sp3 was dominant over the stimulatory effect of Sp1 on transcriptional activity of GLUT1 gene. Furthermore, abolition of Sp3 binding to the proximal promoter of GLUT1 gene completely blocked the response to Sp3.