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Chapter category: Gene Expression

From Gene to Oncogenesis, the Example of Ets Transcription Factors from the PEA3 Group

Chapter authors:
Sébastien Mauen, Jean-Luc Baert and Yvan de Launoit

The PEA3 group of Ets transcription factors is composed of three highly conserved members: Erm, Er81 and Pea3. They regulate transcription of their target genes following post-translational modifications such as phosphorylation, acetylation, sumoylation and ubiquitinylation. Among their target genes are several matrix metalloproteases (MMP) which are enzymes degrading extracellular matrix during normal remodelling events and cancerous metastasis process. In fact, PEA3 group members are often overexpressed in different types of cancers which also overexpress these MMP and present a disseminating phenotype. This suggests that they play a key role in metastasis. The ets genes are found in the majority of known multi-cellular organisms.1,2 They encode a family of transcription factors including more than 30 members, which are, in the most cases, transcriptional activators, and in some rare exceptions, transcriptional repressors.3 These transcription factors share a conserved motif of 85 amino acids, the ETS domain, which is the signature of the family.3 This domain permits the transcription factors to bind DNA on a sequence of 9 nucleotides with the central consensus core 5'-GGAA/T-3': the “ETS Binding Site” (EBS).1 The sequences flanking this central motif determine the binding specificity for each of the Ets family members.4,5 Philogenetically, this transcription factor family is classified in 13 groups according to sequence alignment of the ETS domain, the position of this domain in the protein and the presence of other specific conserved functional domains.6

Sébastien Mauen

Jean-Luc Baert

Yvan de Launoit
Université de Lille I, Institut Pasteur de Lille, Institut de Biologie de Lille

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