ACTIVATION OF THE C-FOS SRE THROUGH SAP-1A

TCFs, which are members of the Ets family of transcription factors, ar e 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-la, displays a significant level of autonomous binding to the SRE Ets box, in contra st to previous observations, deletion of the SRF binding domain did no t modulate the autonomous binding of SAP-la. Also, the autonomous bind ing was not modulated by the phosphorylation of SAP-la by MAP kinases, The autonomous binding was also detected in live cells: transfected S AP-la was able to restore the response of a CArG-less SRE in PC12 cell s. The response occurred in the absence of SRF recruitment since a mut ant of SAP-la in which the B-box, a domain required for interaction wi th SRF, had been deleted was still able to transactivate the CArG-less SRE. The transactivation was repressed by a Ras transdominant negativ e mutant, indicating the involvement of the Ras/MAP kinase pathway. Ta ken together, these data demonstrate that SAP-la is capable of binding to the c-fos SRE in the absence of SRF.