DIDEHYDRORETINOIC ACID - RETINOID RECEPTOR-MEDIATED TRANSCRIPTIONAL ACTIVATION AND BINDING-PROPERTIES

All-trans-3,4-Didehydroretinoic acid (vitamin A(2) acid; DDRA) is one of the retinoids present in human skin, the most responsive tissue to retinoid treatment. To understand the mechanism of action of DDRA in t he control of differentiation and tumorigenesis, we studied its intera ction with cellular retinoic acid-binding proteins (CRABPs) and nuclea r all-trans-retinoic acid (RA) receptors (RARs), and 9-cis-retinoic ac id receptors (RXRs). The IC50 plots of DDRA for inhibition of [H-3]RA binding to CRABP I and II and to RAR alpha, beta and gamma illustrate that this retinoid binds with the same affinity as RA to these protein s. DDRA, however, showed higher affinity than RA. for RXR alpha. Evalu ation of the transcriptional activation potential of DDRA in CV-1 cell s showed that this retinoid induced RAR alpha-mediated transcription t o the same magnitude as RA in the 10(-9) to 10(-6) M concentration ran ge. However, in comparison to RA, DDRA produced a 2- to 3-fold higher activation of the transcription mediated by RXR alpha homodimers, as w ell as RAR beta-RXR alpha heterodimers. These results suggest that the biological activity of retinoids in the skin may be attained through the joint potential of both RA and DDRA. (C) 1997 Elsevier Science Inc .