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. 2012 Jul-Sep;3(3):154-8.
doi: 10.4161/sgtp.19630. Epub 2012 Jun 1.

RAS/ERK pathway transcriptional regulation through ETS/AP-1 binding sites

Peter C Hollenhorst  1
Affiliations

RAS/ERK pathway transcriptional regulation through ETS/AP-1 binding sites

Peter C Hollenhorst. Small GTPases. 2012 Jul-Sep.

Abstract

The RAS/RAF/MEK/ERK signaling pathway is activated by mutation in many cancers. Neighboring ETS and AP-1 DNA binding sequences can act as response elements for transcriptional activation by this pathway. ERK phosphorylation of an ETS transcription factor is one mechanism of activating the RAS/ERK gene expression program that can promote cancer cell phenotypes such as proliferation, invasion, and metastasis. Recent genome-wide mapping of ETS proteins over-expressed by chromosomal rearrangement in prostate cancer reveals a second mechanism for activation of this gene expression program. An oncogenic subset of ETS transcription factors can activate RAS/ERK target genes even in the absence of RAS/ERK pathway activation by binding ETS/AP-1 sequences. Thus, regulation of cancer cell invasion and metastasis via ETS/AP-1 sequence elements depends on which ETS protein is bound, and the status of the RAS/ERK pathway. This commentary will focus on what is known about the selectivity of ETS/AP-1 sequences for different ETS transcription factors and the transcriptional consequences of ETS protein selection.

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  • Hollenhorst PC, Ferris MW, Hull MA, Chae H, Kim S, Graves BJ. Oncogenic ETS proteins mimic activated RAS/MAPK signaling in prostate cells. Genes Dev. 2011;25:2147–57. doi: 10.1101/gad.17546311.

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