Vitamin D-interacting protein 205 (DRIP205) coactivation of estrogen receptor α (ERα) involves multiple domains of both proteins

Abstract

Vitamin D-interacting protein 205 (DRIP205) is a mediator complex protein that anchors the complex to the estrogen receptor (ER) and other nuclear receptors (NRs). Ia ZR-75 breast cancer cells treated with 17β-estradiol (E2) and transfected with a construct containing three tandem estrogen responsive elements (pERE3), DRIP205 coactivates ERα-mediated transactivation. DRIP205Δ587-636 is a DRIP205 mutant in which both NR boxes within amino acids 587-636 have been deleted and, in parallel transfection studies, DRIP205Δ587-636 also coactivates ERα. Moreover, both wild-type and variant DRIP205 also colocalize with ERα in the nuclei of transfected cells. Extensive deletion analysis of DRIP205 shows that multiple domains of this protein play a role in coactivation of ERα and in interactions with ERα. Coactivation of ERα by DRIP205 does not require NR boxes, and variants with deletion of N-terminal (amino acids 1-639) and C-terminal (amino acids 576-1566) significantly coactivate ERα. DRIP205 resembles p160 coactivators that also interact with multiple regions of ERα; however, unlike p160 coactivators, DRIP205 coactivation of ERα does not require NR boxes.