Abstract
The ternary complex factors (TCF) are a subfamily of ETS domain transcription factors that bind and activate serum response elements (SREs) in the promoters of target genes in a ternary complex with a second transcription factor, serum response factor (SRF). Here, we have identified the SRF gene as a target for the TCFs, thereby providing a positive feedback loop whereby TCF activation leads to the enhancement of the expression of its partner protein SRF. The binding of the TCF Elk-1 to the SRF promoter and subsequent regulation of SRF expression occurs in a ternary complex-dependent manner. Our data therefore reveal that SRF is an important target for the ERK and Rho signaling pathways that converge on a ternary TCF-SRF complex at the SRE on the SRF promoter.
Highlights
Elk-1, SAP-1, and SAP-2/ERP/Net comprise the ternary complex factor (TCF)1 subfamily of ETS-domain transcription factors
Upon induction of its expression with ponasterone A (PA), this fusion protein is expected to be recruited to all ternary complex factors (TCF)-dependent promoters and ablate the expression of genes normally controlled by TCFs
The TCF transcription factors play an important role in transducing extracellular signals into a nuclear response by acting as targets for the mitogen-activated protein kinase signaling pathways
Summary
Elk-1, SAP-1, and SAP-2/ERP/Net comprise the ternary complex factor (TCF) subfamily of ETS-domain transcription factors (reviewed in Refs. 1 and 2). These proteins form ternary complexes on target promoters together with the MADS-box protein, serum response factor (SRF). In the case of MAL, this interaction permits linkage of the MAL-SRF complex to the Rho signaling pathway and subsequent activation of SRF-dependent gene expression [13, 16]. SRF appears to aid TCF recruitment, but the reciprocal situation appears to operate on other genes such as nur where the TCFs recruit SRF to the promoter [22, 23] It is currently unclear if the TCFs act in an SRF-independent manner evidence has been gathered to suggest such a role on genes encoding tumor necrosis factor-␣ [24] and 9E3/cCAF [25]. Elk-1 works through a ternary complex with SRF on the SRF promoter, thereby providing a link to the ERK signaling pathway in addition to the well characterized link to the Rho pathway that acts through SRF on its own promoter
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