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 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.
Delva
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Laboratoire de Biologie Cellulaire Hématopoïétique, EP-107 CNRS, Université D. Diderot-Paris VII, Institut d'Hématologie, Hôpital Saint-Louis, 75010 Paris, France.
Bastie
J N
JN
Rochette-Egly
C
C
Kraïba
R
R
Balitrand
N
N
Despouy
G
G
Chambon
P
P
Chomienne
C
C
D001854:Bone Marrow Cells; D001943:Breast Neoplasms / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D020218:Response Elements; D047488:Retinoid X Receptors; D015398:Signal Transduction; D018243:Teratocarcinoma / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C082928:retinoic acid binding protein II, cellular