The 9aaTAD Transactivation Domains: From Gal4 to p53.

Martin Piskacek,Marek Havelka,Andrea Knight,Martina Rezacova,Sumitra Deb

doi:10.1371/journal.pone.0162842

Abstract

The family of the Nine amino acid Transactivation Domain, 9aaTAD family, comprises currently over 40 members. The 9aaTAD domains are universally recognized by the transcriptional machinery from yeast to man. We had identified the 9aaTAD domains in the p53, Msn2, Pdr1 and B42 activators by our prediction algorithm. In this study, their competence to activate transcription as small peptides was proven. Not surprisingly, we elicited immense 9aaTAD divergence in hundreds of identified orthologs and numerous examples of the 9aaTAD species' convergence. We found unforeseen similarity of the mammalian p53 with yeast Gal4 9aaTAD domains. Furthermore, we identified artificial 9aaTAD domains generated accidentally by others. From an evolutionary perspective, the observed easiness to generate 9aaTAD transactivation domains indicates the natural advantage for spontaneous generation of transcription factors from DNA binding precursors.

Highlights

The transcription factors are versatile regulators of gene expression
We have reported that the first transactivation domain of the p53 protein has the highest similarity to the 9aaTAD of the transcription factor E2A, while the second transactivation domain of p53 has the highest similarity to the 9aaTAD of transcription factor MLL [16]
In recent study (Piskacek et al, 2016), we reported artificial 9aaTAD domains identified by online 9aaTAD prediction in Gal4 TAD replicas G80BP-A and G80BP-B originally shown in [25]

Summary

Introduction

The transcription factors are versatile regulators of gene expression. Their DNA binding domains, DBD, recognize regulatory elements and their transactivation domains, TAD, mediate activation of transcription. A number of tested TADs is functional in both yeast and mammals e.g. Gal and p53 transcription factors [1,2]. The Nine amino acid Transactivation Domain, 9aaTAD, is universally recognized by the transcriptional machinery in eukaryotes. We and others have shown the 9aaTAD domains have competence to activate transcription as small peptides [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. We have established the 9aaTAD prediction service online (www.piskacek.org). The 9aaTADs are annotated on protein database UniProt (www.uniprot.org/9aaTAD)

Objectives

Methods

Results

Conclusion