Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II.
Ligand-induced transcription activation of retinoic acid (RA) target genes by nuclear receptors (retinoic acid (RAR) and retinoid X (RXR) receptors) depends on the recruitment of coactivators. We have previously demonstrated that the small 15-kDa cellular RA-binding protein II (CRABPII) is a coactivator present in the RA-dependent nuclear complex. As identifying cell-specific partners of CRABPII might help to understand the novel control of RA signaling, we performed a yeast two-hybrid screen of a hematopoietic HL-60 cDNA library using human CRABPII as bait and have subsequently identified human cyclin D3 as a partner of CRABPII. Cyclin D3 interacted with CRABPII in a ligand-independent manner and equally bound RAR alpha, but not RXR alpha, and only in the presence of RA. We further show that cyclin D3 positively modulated RA-mediated transcription through CRABPII. Therefore, cyclin D3 may be part of a ternary complex with CRABPII and RAR. Finally, we show that cyclin D3 expression paralleled HL-60 differentiation and arrest of cell growth. These findings led us to speculate that control of cell proliferation during induction of differentiation may directly involve, at the transcriptional level, nuclear receptors, coactivators, and proteins of the cell cycle in a cell- and nuclear receptor-specific manner.
Despouy
Gilles
G
Laboratoire de Biologie Cellulaire Hématopoiétique, Equipe Mixte Inserm 00-03, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, Paris 75010, USA.
Bastie
Jean-Nöel
JN
Deshaies
Sylvie
S
Balitrand
Nicole
N
Mazharian
Alexandra
A
Rochette-Egly
Cécile
C
Chomienne
Christine
C
Delva
Laurent
L
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D056743:Cyclin D3; D016213:Cyclins / Q000737:chemistry / Q000502:physiology*; D017931:DNA Primers; D018922:HL-60 Cells; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D011817:Rabbits; D018168:Receptors, Retinoic Acid / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D014162:Transfection; D014212:Tretinoin / Q000494:pharmacology*
D000906:Antibodies; D000911:Antibodies, Monoclonal; C534696:CCND3 protein, human; D002352:Carrier Proteins; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D017931:DNA Primers; D008024:Ligands; D046911:Macromolecular Substances; D018168:Receptors, Retinoic Acid; D011994:Recombinant Proteins; C082928:retinoic acid binding protein II, cellular; D014212:Tretinoin