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J Steroid Biochem Mol Biol. 2019 Mar;187:118-123. doi: 10.1016/j.jsbmb.2018.11.008. Epub 2018 Nov 20.

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

Author information

1
Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Czech Republic; Laboratory of Cancer Biology and Genetics, Czech Republic; Gamma Delta T Cell Laboratory, Czech Republic. Electronic address: piskacek@med.muni.cz.
2
Department of Pathological Physiology, Faculty of Medicine, Masaryk University Brno, Czech Republic; Laboratory of Cancer Biology and Genetics, Czech Republic; Gamma Delta T Cell Laboratory, Czech Republic.

Abstract

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.

KEYWORDS:

9aaTAD; CBP; HNF4; KIX; MED15; PPAR; RARa; VDL

PMID:
30468856
DOI:
10.1016/j.jsbmb.2018.11.008
[Indexed for MEDLINE]

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