title: Regulation of the c-fos promoter by the ternary complex factor Sap-1a and its coactivator CBP.
abstract: The c-fos proto-oncogene is activated by a plethora of signals via the transcription factors Sap-1a and CREB. Recently, the coactivator CBP has been demonstrated to act in concert with CREB when CREB is phosphorylated by protein kinase A. We show that CBP also binds directly to Sap-1a. While phosphorylation of Sap-1a by mitogen-activated protein kinases is not necessary for CBP/Sap-1a interaction, functional cooperation between these two proteins requires Sap-1a to become phosphorylated. CBP-antagonists impair Sap-1a-mediated transactivation. Similarly, the CBP antagonist E1A suppresses c-fos upregulation by phosphorylated CREB, indicating that CBP is a central component of c-fos regulation. Furthermore, CBP is phosphorylated by protein kinase A in vitro and the transactivation potential of the carboxy-terminal region of CBP is enhanced in the presence of active protein kinase A in vivo. Thus, CBP, in addition to CREB, is a target for cAMP-dependent signaling. However, combined phosphorylation of CBP by protein kinase A and mitogen-activated protein kinases appears to be non-cooperative, suggesting that CBP serves the function of a dampening integrator of two different signaling pathways.
authors.affiliation: Institute for Molecular Biology, Hannover Medical School, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Janknecht
authors.forename: A
authors.initials: A
authors.lastname: Nordheim
mesh_terms: D000818:Animals; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016762:Genes, fos; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011817:Rabbits; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D015534:Trans-Activators; D017868:Cyclic AMP-Dependent Protein Kinases