title: Activation of the c-fos SRE through SAP-1a.
abstract: TCFs, which are members of the Ets family of transcription factors, are recruited to the Serum Response Element (SRE) in the c-fos promoter by SRF. These Ets proteins, which are substrates for the MAP kinases, are direct targets of the Ras/MAP kinase signal transduction pathway. In this paper, we demonstrate that one of the TCFs, SAP-1a, displays a significant level of autonomous binding to the SRE Ets box. In contrast to previous observations, deletion of the SRF binding domain did not modulate the autonomous binding of SAP-1a. Also, the autonomous binding was not modulated by the phosphorylation of SAP-1a by MAP kinases. The autonomous binding was also detected in live cells: transfected SAP-1a was able to restore the response of a CArG-less SRE in PC12 cells. The response occurred in the absence of SRF recruitment since a mutant of SAP-1a in which the B-box, a domain required for interaction with SRF, had been deleted was still able to transactivate the CArG-less SRE. The transactivation was repressed by a Ras transdominant negative mutant, indicating the involvement of the Ras/MAP kinase pathway. Taken together, these data demonstrate that SAP-1a is capable of binding to the c-fos SRE in the absence of SRF.
authors.affiliation: Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Institut Gustave Roussy, Villejuif, France.
authors.forename: H
authors.initials: H
authors.lastname: Masutani
authors.forename: L
authors.initials: L
authors.lastname: Magnaghi-Jaulin
authors.forename: S
authors.initials: S
authors.lastname: Ait-Si-Ali
authors.forename: R
authors.initials: R
authors.lastname: Groisman
authors.forename: P
authors.initials: P
authors.lastname: Robin
authors.forename: A
authors.initials: A
authors.lastname: Harel-Bellan
authors.forename: S
authors.initials: S
authors.lastname: Ait Si Ali
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D016762:Genes, fos; D009687:Nuclear Proteins / Q000378:metabolism; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D011994:Recombinant Proteins; D012045:Regulatory Sequences, Nucleic Acid; D026362:Serum Response Factor; D014162:Transfection; D050808:ets-Domain Protein Elk-4
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D026362:Serum Response Factor; D050808:ets-Domain Protein Elk-4; D017871:Calcium-Calmodulin-Dependent Protein Kinases