Piskacek Martin, Havelka Marek, Rezacova Martina, Knight Andrea
Laboratory of Cancer Biology and Genetics, Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic.
Gamma Delta T Cell Laboratory, Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic.
PLoS One. 2016 Sep 12;11(9):e0162842. doi: 10.1371/journal.pone.0162842. eCollection 2016.
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.
九氨基酸反式激活结构域(9aaTAD)家族目前包含40多个成员。从酵母到人类,转录机制都能普遍识别9aaTAD结构域。我们通过预测算法在p53、Msn2、Pdr1和B42激活因子中鉴定出了9aaTAD结构域。在本研究中,证实了它们作为小肽激活转录的能力。不出所料,我们在数百个已鉴定的直系同源物中发现了9aaTAD的巨大差异以及9aaTAD物种趋同的众多例子。我们发现哺乳动物p53与酵母Gal4 9aaTAD结构域存在意想不到的相似性。此外,我们还鉴定出了其他人意外产生的人工9aaTAD结构域。从进化的角度来看,观察到的生成9aaTAD反式激活结构域的容易程度表明了从DNA结合前体自发产生转录因子的天然优势。