AP-2 enhances Sp1-dependent activation of the growth-regulated human ATP/ADP translocator.
The mammalian ATP/ADP translocator isoform-2 (ANT2) gene is growth-activated. Regulation of the gene appears to involve Sp1, as an essential activator, and a suppressor through an Sp1 core element next to the transcription start. We show here that the proximal promoter also binds AP-2 strongly and specifically to two sites, one of which overlaps the Sp1 proximal suppressor site. AP-2 binds with an affinity of 10 to15 fold higher than that of Sp1. AP-2 alone does not alter the ANT2 promoter activity in transfected SL2 cells, but enhances the Sp1-dependent activation of the promoter several fold. Enhancement by AP-2 is observed only when Sp1 is limiting for transcription activation. These data suggest that the cellular AP-2/Sp1 ratio might influence ANT2 expression in developing or differentiating cells.
Department of Biochemistry, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, S-106 91 Sweden. li@mail.biokemi.su.se
R
R
Li
Z
Z
Hodny
A
A
Zaid
P
P
Barath
B D
BD
Nelson
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D000226:Mitochondrial ADP, ATP Translocases / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D011994:Recombinant Proteins; D016329:Sp1 Transcription Factor; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D000226:Mitochondrial ADP, ATP Translocases; D003850:Deoxyribonuclease I