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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 RAR
and RXR
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 RXR
-RAR
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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