Sp1-like proteins function in the transcription of human ferredoxin genes.
We characterized a regulatory element located in the -76 to -62 region of the human ferredoxin gene. This region bound to Sp1-like proteins with low affinity, as shown using electrophoretic mobility shift, competition, antibody binding, and Southwestern experiments. The similarity of the regulatory element to Sp1 extends beyond its DNA-binding domain, as cloned Sp1 functioned equally well when fused to a peptide that bound to an irrelevant site. The function of these Sp1-binding sites is mediated through the cAMP-dependent protein kinase (PKA) signaling pathway, because reporter genes downstream of the Sp1-binding sites were not activated in a PKA-deficient cell line. Transfection of the catalytic subunit of PKA restored activated transcription. Similar Sp1-binding sites identified in the CYP11A1 and CYP21 genes also controlled cAMP-dependent transcription of the reporter gene. Our finding of the function of Sp1-like proteins in steroidogenic gene transcription adds one more role Sp1 plays in controlling physiological events.
Yeh
J R
JR
Institute of Molecular Biology, Academia Sinica, Nankang, Taiwan, Republic of China.
Hsu
L C
LC
Chung
B c
Bc
D000302:Adrenal Cortex / Q000378:metabolism*; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005288:Ferredoxins / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D015290:Second Messenger Systems / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000502:physiology*; D013255:Steroid 21-Hydroxylase / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D005288:Ferredoxins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D005576:Colforsin; D000242:Cyclic AMP; D013255:Steroid 21-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017868:Cyclic AMP-Dependent Protein Kinases