Phosphorylation at serine 208 of the 1α,25-dihydroxy Vitamin D3 receptor modulates the interaction with transcriptional coactivators

被引:22
作者
Arriagada, Gloria
Paredes, Roberto
Olate, Juan
van Wijnen, Andre
Lian, Jane B.
Stein, Gary S.
Stein, Janet L.
Onate, Sergio
Montecino, Martin
机构
[1] Univ Concepcion, Fac Ciencias Biol, Dept Bioquim & Biol Mol, Concepcion, Chile
[2] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA
[3] Roswell Pk Canc Ctr, Dept Urol Oncol, Buffalo, NY 14263 USA
关键词
1; alpha; 25-dihydroxy Vitamin D3 receptor; coactivators; transcription;
D O I
10.1016/j.jsbmb.2006.12.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Upon ligand bindina the 1 alpha.25-dihydroxy Vitamin D3 receptor (VDR) undergoes a conformational change that allows interaction with coactivator proteins including p160/SRC family members and the multimeric DRIP complex through the DRIP205 subunit. Casein kinase II (CKII) phosphorylates VDR both in vitro and in vivo at serine 208 within the hinge domain. This phosphorylation does not affect the ability of VDR to bind DNA. but increases its ability to transactivate target promoters. Here, we have analyzed whether phosphorylation of VDR by CKII modulates the ability of VDR to interact with coactivators in vitro. We find that both mutation of serine 208 to aspartic acid (VDRS208D) or phosphorylation of VDR by CKII enhance the interaction of VDR with DRIP205 in the presence of 1 alpha,25-dihydroxy Vitamin D3. We also find that the mutation VDRS208D neither affects the ability of this protein to bind DNA nor to interact with SRC-1 and RXRU. Together, our results indicate that phosphorylation of VDR at serine 208 contributes to modulate the affinity of VDR for the DRIP complex and therefore may have a role in vivo regulating VDR-mediated transcriptional enhancement. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:425 / 429
页数:5
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