An evolutionary, structural and functional overview of the mammalian TEAD1 and TEAD2 transcription factors

• TEAD proteins constitute a family of highly conserved transcription factors.
• TEAD1/2 have a crucial role during embryonic development.
• TEAD1/2 regulate organ formation, cell death and proliferation.
• TEAD1/2 are deregulated in several types of cancer.
• TEAD1/2 could constitute good candidates for therapeutic targets.

TEAD proteins constitute a family of highly conserved transcription factors, characterized by a DNA-binding domain called the TEA domain and a protein-binding domain that permits association with transcriptional co-activators. TEAD proteins are unable to induce transcription on their own. They have to interact with transcriptional cofactors to do so. Once TEADs bind their co-activators, the different complexes formed are known to regulate the expression of genes that are crucial for embryonic development, important for organ formation (heart, muscles), and involved in cell death and proliferation. In the first part of this review we describe what is known of the structure of TEAD proteins. We then focus on two members of the family: TEAD1 and TEAD2. First the different transcriptional cofactors are described. These proteins can be classified in three categories: i), cofactors regulating chromatin conformation, ii), cofactors able to bind DNA, and iii), transcriptional cofactors without DNA binding domain. Finally we discuss the recent findings that identified TEAD1 and 2 and its coactivators involved in cancer progression.