Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex

Two sorts of proteins bind to, and mediate the developmental and homeostati c effects of, retinoic acid (RA): the RAR and RXR nuclear receptors, which act as ligand-dependent transcriptional regulators, and the cellular RA bin ding proteins (CRABPI and CRABPII). CRABPs are generally known to be implic ated in the synthesis, degradation, and control of steady-state levels of R A, get previous and recent data have indicated that they could play a role in the control of gene expression. Here we show for the first time that, bo th in vitro and in vivo, CRABPII is associated with RAR alpha and RXR alpha in a ligand-independent manner in mammalian cells (HL-60, NB-4, and MCF-7) , In the nucleus, this protein complex binds the RXR-RAR-specific response element of an RA target gene (RARE-DR5). Moreover, in the presence of retin oids that bind both the nuclear receptors and CRABPII, enhancement of trans activation by RXR alpha-RAR alpha heterodimers is observed in the presence of CRABPII. Thus, CRABPII appears to be a novel transcriptional regulator i nvolved in RA signaling.