Induction of proto-oncogene fos transcription through the adenylate cyclase pathway: characterization of a cAMP-responsive element.

P Sassone-Corsi, J Visvader, L Ferland… - Genes & …, 1988 - genesdev.cshlp.org
P Sassone-Corsi, J Visvader, L Ferland, PL Mellon, IM Verma
Genes & development, 1988genesdev.cshlp.org
Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We
report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells
(PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate
cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-
1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position-
60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE) …
Abstract
Transcription of proto-oncogene fos is induced by elevated levels of intracellular cAMP. We report that human c-fos promoter recombinants transfected into rat pheochromocytoma cells (PC12) and human choriocarcinoma cells (JEG-3) are induced by stimulation of adenylate cyclase and that this induction is diminished considerably in the mutant PC12 cell line A126-1B2, which is deficient in cAMP-dependent protein kinase II. An element centered at position-60 of the c-fos promoter, which encompasses a consensus cAMP response element (CRE), is sufficient to confer cAMP responsiveness to a herpes thymidine kinase/CAT fusion gene. The specific binding of a nuclear protein to the c-fos CRE can be competed by the somatostatin and alpha-chorionic gonadotropin (alpha-CG) promoter regions that contain CREs. Gel mobility shift assays with double-stranded oligonucleotides containing either the wild-type or mutated c-fos CRE sequence have demonstrated that binding occurs only to the wild-type CRE. The nuclear factor binding to the c-fos CRE is likely to be transcription factor CREB (CRE nuclear binding protein), because an affinity-purified 43-kD CREB isolated from PC12 cells binds efficiently in a DNA footprinting assay. Thus, regulation of the c-fos gene transcription appears to involve a mechanism common to many genes that respond to cAMP as a second message leading to cell growth and differentiation.
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