Okadaic acid stimulates H ferritin transcription in HeLa cells by increasing the interaction between the p300 CO-activator molecule and the transcription factor Bbf.
The transcription of the human H ferritin gene is regulated by a transcription factor, called Bbf, which binds an enhancer element located in the -100/+1 region of the H promoter. To evaluate a possible role of Bbf phosphorylation on the promoter efficiency, we exposed HeLa cells to the phosphatase inhibitor okadaic acid (OA). The okadaic acid treatment increased about 4-fold the transcription driven by the -100/+1 region of the H promoter. However, the DNA binding activity of Bbf was not modified by OA, as assessed by EMSA. Immunoprecipitation experiments demonstrated that the OA-treatment stimulates and/or stabilizes the complex between Bbf and the nuclear protein p300, most probably by inducing the phosphorylation state of the complex. Bbf depends on the p300 molecule to trigger RNA polymerase II and thus transcription of the H ferritin gene.
Bevilacqua
M A
MA
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Italy.
Faniello
M C
MC
Cimino
F
F
Costanzo
F
F
D051699:Cyclic AMP Response Element-Binding Protein A; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins; D005293:Ferritins / Q000187:drug effects / Q000235:genetics*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D046911:Macromolecular Substances; D056921:Nuclear Receptor Coactivator 3; D019319:Okadaic Acid / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*
C073555:CrebA protein, Drosophila; D051699:Cyclic AMP Response Element-Binding Protein A; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046911:Macromolecular Substances; D015534:Trans-Activators; D014157:Transcription Factors; D019319:Okadaic Acid; D004247:DNA; D005293:Ferritins; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3