Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid–Activated Receptor
2008

COUP-TFII: A Low-Affinity Retinoic Acid Receptor

publication Evidence: moderate

Author Information

Author(s): Kruse SW, Suino-Powell K, Zhou XE, Kretschman JE, Reynolds R, Vonrhein C, Xu Y, Wang L, Tsai SY, Tsai MJ, Xu H

Primary Institution: Van Andel Research Institute

Hypothesis

Is COUP-TFII a ligand-regulated nuclear receptor activated by retinoic acids?

Conclusion

COUP-TFII is a ligand-regulated nuclear receptor that can be activated by retinoic acids, although the concentrations required are higher than physiological levels.

Supporting Evidence

  • The crystal structure of COUP-TFII reveals an autorepressed conformation that blocks coactivator binding.
  • Retinoic acids can promote COUP-TFII to recruit coactivators and activate transcription.
  • COUP-TFII exhibits constitutive transcriptional activity in multiple cell lines.

Takeaway

COUP-TFII is like a switch that can be turned on by certain chemicals called retinoic acids, but it needs a lot more of them than what is usually found in our bodies.

Methodology

The study involved crystallography to determine the structure of COUP-TFII and cell-based assays to assess its transcriptional activity.

Limitations

The concentrations of retinoic acids required for COUP-TFII activation are significantly higher than physiological levels, suggesting they may not be the natural ligands.

Digital Object Identifier (DOI)

10.1371/journal.pbio.0060227

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