C/EBPBeta and Elk-1 synergistically transactivate the c-fos serum response element

被引:22
作者
Hanlon M. [1 ]
Bundy L.M. [1 ]
Sealy L. [1 ]
机构
[1] Dept. of Molec. Physiol./Biophysics, Vanderbilt Univ. School of Medicine, Nashville, TN
关键词
Serum Response Factor; Chloramphenicol Acetyl Transferase; Serum Response Element; Pulldown Assay; Chloramphenicol Acetyl Transferase Activity;
D O I
10.1186/1471-2121-1-2
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学科分类号
摘要
Background: The serum response element (SRE) in the c-fos promoter is a convergence point for several signaling pathways that regulate induction of the c-fos 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. Results: 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 in vitro GST-pulldown assay and in an in vivo co-immunoprecipitation assay. The in vivo 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. Conclusions: 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 c-fos SRE in response to mitogenic signaling by Ras.
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