Nuclear hormone receptors: Ancient 9aaTAD and evolutionally gained NCoA activation pathways

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Authors

PISKÁČEK Martin HAVELKA Marek JENDRUCHOVÁ Kristína KNIGHT Andrea

Year of publication 2019
Type Article in Periodical
Magazine / Source Journal of steroid biochemistry and molecular biology
MU Faculty or unit

Faculty of Medicine

Citation
Web http://dx.doi.org/10.1016/j.jsbmb.2018.11.008
Doi http://dx.doi.org/10.1016/j.jsbmb.2018.11.008
Keywords 9aaTAD; CBP; HNF4; KIX; MED15; PPAR; RARa; VDL
Description In higher metazoans, the nuclear hormone receptors activate transcription trough their specific adaptors, nuclear hormone receptor adaptors NCoA, which are absent in lower metazoans. The Nine amino acid TransActivation Domain, 9aaTAD, was reported for a large number of the transcription activators that recruit general mediators of transcription. In this study, we demonstrated that the 9aaTAD from NHR-49 receptor of nematode C.elegans activates transcription as a small peptide. We showed that the ancient 9aaTAD domains are conserved in the nuclear hormone receptors including human HNF4, RARa, VDR and PPARg. Also their small 9aaTAD peptides effectively activated transcription in absence of the NCoA adaptors. We also showed that adjacent H11 domains in ancient and modern hormone receptors have an inhibitory effect on their 9aaTAD function.
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