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Review
. 2012 Aug;1826(1):1-12.
doi: 10.1016/j.bbcan.2012.02.002. Epub 2012 Mar 8.

ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors

Sangphil Oh  1 , Sook Shin, Ralf Janknecht
Affiliations
Review

ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors

Sangphil Oh et al. Biochim Biophys Acta. 2012 Aug.

Abstract

The homologous ETV1, ETV4 and ETV5 proteins form the PEA3 subfamily of ETS transcription factors. In Ewing tumors, chromosomal translocations affecting ETV1 or ETV4 are an underlying cause of carcinogenesis. Likewise, chromosomal rearrangements of the ETV1, ETV4 or ETV5 gene occur in prostate tumors and are thought to be one of the major driving forces in the genesis of prostate cancer. In addition, these three ETS proteins are implicated in melanomas, breast and other types of cancer. Complex posttranslational modifications govern the activity of PEA3 factors, which can promote cell proliferation, motility and invasion. Here, we review evidence for a role of ETV1, 4 and 5 as oncoproteins and describe modes of their action. Modulation of their activation or interaction with cofactors as well as inhibiting crucial target gene products may ultimately be exploited to treat various cancers that are dependent on the PEA3 group of ETS transcription factors.

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Figures

Fig. 1
Fig. 1
(A) Scheme of the three human PEA3 ETS transcription factors. Acidic domains are highlighted in grey and the ETS DNA-binding domain in black. (B) Alignment of amino acid sequences. The following human proteins are shown: ETV1 (GenBank ID: NP_004947.2), ETV4 (GenBank ID: NP_001977.1) and ETV5 (GenBank ID: NP_004445.1). Identical amino acids are indicated (+). Acidic domains are boxed, and the ETS motif represented with white letters on black background. Posttranslational modifications that were experimentally confirmed are highlighted: modification of serine/threonine residues by MAPK, MAPKAPK or PKA (please note that MAPKAPK sites are likely also targeted by PKA); attachment of SUMO to lysine residues (please note that K322 in ETV4 is a minor in vitro sumoylation site and likely not sumoylated in vivo); and acetylation (Ac) of lysine residues by p300 (only the four most important ETV4 acetylation sites are shown, which happen to overlap with its sumoylation sites).
Fig. 2
Fig. 2
Potential avenues of inhibiting PEA3 factor action.
See this image and copyright information in PMC

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