Pijnappel W W, Folkers G E, de Jonge W J, Verdegem P J, de Laat S W, Lugtenburg J, Hendriks H F, van der Saag P T, Durston A J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15424-9. doi: 10.1073/pnas.95.26.15424.
We report identification of 9-cis-4-oxo-retinoic acid (9-cis-4-oxo-RA) as an in vivo retinoid metabolite in Xenopus embryos. 9-Cis-4-oxo-RA bound receptors (RARs) alpha, beta, and gamma as well as retinoid X receptors (RXRs) alpha, beta, and gamma in vitro. However, this retinoid displayed differential RXR activation depending on the response pathway used. Although it failed to activate RXRs in RXR homodimers, it activated RXRs and RARs synergistically in RAR-RXR heterodimers. 9-Cis-4-oxo-RA thus acted as a dimer-specific agonist. Considering that RAR-RXR heterodimers are major functional units involved in transducing retinoid signals during embryogenesis and that 9-cis-4-oxo-RA displayed high potency for modulating axial pattern formation in Xenopus, metabolism to 9-cis-4-oxo-RA may provide a mechanism to target retinoid action to this and other RAR-RXR heterodimer-mediated processes.
我们报告了在非洲爪蟾胚胎中鉴定出9-顺式-4-氧代视黄酸（9-cis-4-oxo-RA）作为一种体内类视黄醇代谢产物。9-cis-4-oxo-RA在体外能与视黄酸受体（RARs）α、β和γ以及视黄醇X受体（RXRs）α、β和γ结合。然而，这种类视黄醇根据所使用的反应途径显示出不同的RXR激活情况。尽管它在RXR同二聚体中未能激活RXRs，但在RAR-RXR异二聚体中它能协同激活RXRs和RARs。因此，9-cis-4-oxo-RA作为一种二聚体特异性激动剂。鉴于RAR-RXR异二聚体是胚胎发育过程中参与转导类视黄醇信号的主要功能单位，并且9-cis-4-oxo-RA在调节非洲爪蟾轴向模式形成方面显示出高效能，代谢生成9-cis-4-oxo-RA可能提供一种机制，将类视黄醇作用靶向于此以及其他RAR-RXR异二聚体介导的过程。
