Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity.
D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of 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. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins.
Jian
Yongzhi
Y
State Key Laboratory of Genetic Engineering and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032, PR China.
Yan
Jun
J
Wang
Hanzhou
H
Chen
Chen
C
Sun
Maoyun
M
Jiang
Jianhai
J
Lu
Jieqiong
J
Yang
Yanzhong
Y
Gu
Jianxin
J
D000818:Animals; D001483:Base Sequence; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation / Q000502:physiology
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D056743:Cyclin D3; D016213:Cyclins; D017931:DNA Primers; D008024:Ligands; D018167:Receptors, Calcitriol