| Summary: | <p>Abstract</p> <p>Background</p> <p>The serum response element (SRE) in the <it>c-fos</it> promoter is a convergence point for several signaling pathways that regulate induction of the <it>c-fos</it> gene. Many transcription factors regulate the SRE, including serum response factor (SRF), ternary complex factor (TCF), and CCAAT/enhancer binding protein-beta (C/EBPβ). Independently, the TCFs and C/EBPβ have been shown to interact with SRF and to respond to Ras-dependent signaling pathways that result in transactivation of the SRE. Due to these common observations, we addressed the possibility that C/EBPβ and Elk-1 could both be necessary for Ras-stimulated transactivation of the SRE.</p> <p>Results</p> <p>In this report, we demonstrate that Elk-1 and C/EBPβ functionally synergize in transactivation of both a Gal4 reporter plasmid in concert with Gal4-SRF and in transactivation of the SRE. Interestingly, this synergy is only observed upon activation of Ras-dependent signaling pathways. Furthermore, we show that Elk-1 and C/EBPβ could interact both in an <it>in vitro</it> GST-pulldown assay and in an <it>in vivo</it> co-immunoprecipitation assay. The <it>in vivo</it> interaction between the two proteins is dependent on the presence of activated Ras. We have also shown that the C-terminal domain of C/EBPβ and the N-terminal domain of Elk-1 are necessary for the proteins to interact.</p> <p>Conclusions</p> <p>These data show that C/EBPβ and Elk-1 synergize in SRF dependent transcription of both a Gal-4 reporter and the SRE. This suggests that SRF, TCF, and C/EBPβ are all necessary for maximal induction of the <it>c-fos</it> SRE in response to mitogenic signaling by Ras.</p>
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