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Molecular and Cellular Biology, October 1999, p. 7158-7167, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Physical and Functional Interactions between Cellular Retinoic Acid Binding Protein II and the Retinoic Acid-Dependent Nuclear Complex

Laurent Delva,1 Jean-Noël Bastie,1 Cécile Rochette-Egly,2 Radhia Kraïba,1 Nicole Balitrand,1 Gilles Despouy,1 Pierre Chambon,2 and Christine Chomienne1,*

Laboratoire de Biologie Cellulaire Hématopoïétique, EP-107 CNRS, Université D. Diderot-Paris VII, Institut d'Hématologie, Hôpital Saint-Louis, 75010 Paris,1 and Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP/Collège de France, 67404 Illkirch Cedex, CU de Strasbourg,2 France

Received 8 March 1999/Returned for modification 4 April 1999/Accepted 4 July 1999

Two sorts of proteins bind to, and mediate the developmental and homeostatic effects of, retinoic acid (RA): the RAR and RXR nuclear receptors, which act as ligand-dependent transcriptional regulators, and the cellular RA binding proteins (CRABPI and CRABPII). CRABPs are generally known to be implicated in the synthesis, degradation, and control of steady-state levels of RA, yet 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, both in vitro and in vivo, CRABPII is associated with RARalpha and RXRalpha 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 retinoids that bind both the nuclear receptors and CRABPII, enhancement of transactivation by RXRalpha -RARalpha heterodimers is observed in the presence of CRABPII. Thus, CRABPII appears to be a novel transcriptional regulator involved in RA signaling.

* Corresponding author. Mailing address: Laboratoire de Biologie Cellulaire Hématopoïétique (LBCH), EP-107 CNRS, Université D. Diderot-Paris VII, Institut d'Hématologie, Hôpital Saint-Louis, 75010 Paris, France. Phone: 33 0 1 42 40 97 45. Fax: 33 0 1 42 00 01 60. E-mail: lbch{at}chu-stlouis.fr.

Molecular and Cellular Biology, October 1999, p. 7158-7167, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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