Cyclin D3 Is a Cofactor of Retinoic Acid Receptors, Modulating Their Activity in the Presence of Cellular Retinoic Acid-binding Protein II

• Published in: The Journal of biological chemistry 2003-02, Vol.278 (8), p.6355-6362
• Main Authors: Despouy, G, Bastie, J, Deshaies, S, Balitrand, N, Mazharian, A, Rochette-Egly, C, Chomienne, C, Delva, L
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies, Monoclonal; Base Sequence; Biochemistry, Molecular Biology; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cloning, Molecular; Cyclin D3; Cyclins - chemistry; Cyclins - physiology; DNA Primers; HL-60 Cells; Humans; Life Sciences; Ligands; Macromolecular Substances; Mice; Models, Biological; Molecular Sequence Data; Rabbits; Receptors, Retinoic Acid - drug effects; Receptors, Retinoic Acid - metabolism; Recombinant Proteins - metabolism; Saccharomyces cerevisiae - metabolism; Signal Transduction - drug effects; Transcriptional Activation; Transfection; Tretinoin - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M210697200

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 RARα, but not RXRα, 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.