Cyclin D3 Involved In Transcriptional Regulation, P110c Induced Apoptosis And Activity Of Oligosaccharides

I. The research of the involvement of cyclin D3 in vitamin D dependent transcriptional controlD-type cyclins are essential for the progression through the G1 phase of the cell cycle through their binding to and activation of the cyclin-dependent kinases CDK4 and CDK6. Besides serving as cell cycle regulators, D-type cyclins were reported recently to have transcription regulation functions through interaction with several transcription factors, which in turn affected their activity. Here we found that cyclin D3 is a new interacting partner of Vitamin D-binding protein (DBP), the major transporter of vitamin D which is responsible for transporting it from serum to various target cells. And we also found that cyclin D3 associated with Vitamin D Receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. Cyclin D3 interacted with VDR in a ligand independent manner, but treatment of the ligand, 1, 25-dihydroxyvitamin D3, strengthened the interaction. Cyclin D3 didn't affect cellular distribution of VDR and confocal microscopy analysis showed that ligand activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 positively modulated transcription activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. DBP was also found to interact with VDR in vitro, but the interaction was greatly weakened when VDR was activated by vitamin D. DBP, VDR and cyclin D3 might form a ternary complex in vitro. These findings suggested that cyclin D3 was closely related to vitamin D dependent transcriptional control and provided us a new clue to understand the transcription regulation functions of D-type cyclins.