Activation of the c-fos SRE through SAP-1a.
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.
Masutani
H
H
Laboratoire de Biologie des Tumeurs Humaines, CNRS URA 1156, Institut Gustave Roussy, Villejuif, France.
Magnaghi-Jaulin
L
L
Ait-Si-Ali
S
S
Groisman
R
R
Robin
P
P
Harel-Bellan
A
A
Ait Si Ali
S
S
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
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