INVESTIGADORES
CERUTI Julieta Maria
congresos y reuniones científicas
Título:
EXTENDED ROLE OF UNPHOSPHORYLATED CREB ON GENE EXPRESSION IN ABSENCE OF EXTERNAL STIMULI.
Autor/es:
GRETEL KAMM; JULIETA M. CERUTI; PABLO F. SIRKIN; EDUARDO T. CÁNEPA
Lugar:
Pinamar, Argentina
Reunión:
Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2007
Institución organizadora:
SAIB
Resumen:
Transcription factor CREB induces the activity of CRE-containing gene promoters through PKA-mediated S133 phosphorylation. However, it has been reported that its binding to DNA is independent of such modification. This fact opens a question about the role, if any, of unphosphorylated CREB on gene regulation. By northern blot analysis and transfection experiments in HepG2 cells, we have demonstrated that ALAS basal transcription is diminished by CREB overexpression. This inhibition is stronger after overexpressing a CREB mutant that can not be phosphorylated or by incubating cells with the PKAinhibitor, H89. These results suggest that basal phosphorylation significantly increases the steady state level of ALAS expression. OverexpressingCREBwith a mutation in its DNA-binding domain or a CRE-mutated ALAS promoter, we demonstrated that this inhibitory effect is dependent on the CREB-binding and the presence of CRE sites on the promoter. The H-89 inhibition is released by oligodeoxynucleotide CREB decoy only when wild type CRE-ALAS promoter was used.We selected 30 hepatic genes harboring CRE regulatory regions and reported to be cAMP responsive. Interestingly, several of such genes are repressed by unphosphorylated CREB in a similar way that ALAS did. These results support a widespread role of transcription factor CREB controlling gene expression in the absence of external stimuli.