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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism
  • Hepatocyte Nuclear Factor 4 / chemistry
  • Hepatocyte Nuclear Factor 4 / metabolism
  • Humans
  • Models, Molecular
  • PPAR gamma / chemistry
  • PPAR gamma / metabolism
  • Peptides / chemistry
  • Peptides / metabolism
  • Protein Domains
  • Receptors, Calcitriol / chemistry
  • Receptors, Calcitriol / metabolism
  • Receptors, Cytoplasmic and Nuclear / chemistry
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Retinoic Acid Receptor alpha / chemistry
  • Retinoic Acid Receptor alpha / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Transcriptional Activation*


  • Caenorhabditis elegans Proteins
  • Hepatocyte Nuclear Factor 4
  • NHR-49 protein, C elegans
  • PPAR gamma
  • Peptides
  • RARA protein, human
  • Receptors, Calcitriol
  • Receptors, Cytoplasmic and Nuclear
  • Retinoic Acid Receptor alpha
  • VDR protein, human