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

来源：

BMC Cell Biology | / 1卷 / 1期

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

中图分类号：

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.

引用

共 34 条

[11]

Janknecht R., Nordheim A., Elk-1 protein domains required for direct and SRF-assisted DNA-binding, Nucleic Acids Res., 20, pp. 3317-3324, (1992)

[12]

Shaw P.E., Frasch S., Nordheim A., Repression of c-fos transcription is mediated through p67SRF bound to the SRE, Embo J., 8, pp. 2567-2574, (1989)

[13]

Shaw P.E., Ternary complex formation over the c-fos serum response element: p62TCF exhibits dual component specificity with contacts to DNA and an extended structure in the DNA-binding domain of p67SRF, Embo J., 11, pp. 3011-3019, (1992)

[14]

Rao V.N., Reddy E.S., elk-1 domains responsible for autonomous DNA binding, SRE:SRF interaction and negative regulation of DNA binding, Oncogene, 7, pp. 2335-2340, (1992)

[15]

Treisman R., Marais R., Wynne J., Spatial flexibility in ternary complexes between SRF and its accessory proteins, Embo. J., 11, pp. 4631-4640, (1992)

[16]

Treisman R., Ternary complex factors: Growth factor regulated transcriptional activators, Curr. Opin. Genet. Dev., 4, pp. 96-101, (1994)

[17]

Treisman R., Regulation of transcription by MAP kinase cascades, Curr. Opin. Cell Biol., 8, pp. 205-215, (1996)

[18]

Whitmarsh A.J., Davis R.J., Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways, J. Mol. Med., 74, pp. 589-607, (1996)

[19]

Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T., A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family, Embo J., 9, pp. 1897-1906, (1990)

[20]

Descombes P., Chojkier M., Lichtsteiner S., Falvey E., Schibler U., LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein, Genes Dev., 4, pp. 1541-1551, (1990)

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