Mechanisms of coactivation of estrogen receptor alpha (ER alpha)- and ER alpha/Sp-mediated gene transactivation by vitamin D receptor interacting protein 205 (DRIP205) in breast cancer cells /
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| Format: | Thesis eBook |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University],
[2010]
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| Online Access: | Link to OAK Trust copy |
| 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). In 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. AF1 and AF2 of ERα are both required for DRIP205 coactivation. Extensive deletion analysis of DRIP205 shows that multiple domains of this protein play a role in coactivation of ERα and in interactions with ERα. On the other hand, both DRIP205 and DRIP205Δ587-636 coactivate E2-induced transactivation of ERα/Sp1 in cells transfected with a construct containing three GC-rich sites (pSp13). Coactivation of ERα/Sp1 by DRIP205 is dependent on AF1 of ERα. Enhancement of ERα and ERα/Sp1 by DRIP205 does not require NR boxes of DRIP205, and deletion mutants DRIP205 (1-714) and DRIP205 (516-1566) significantly coactivate ERα and ERα/Sp1. RNA interference study showed that DRIP205 coactivation of ERα/Sp was abolished in cells transfected with iSp3 and iSp4, suggesting that Sp3 and Sp4 are required for coactivation of ERα/Sp by DRIP205 in ZR-75 cells. |
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| Item Description: | "Major Subject: Biochemistry" Title from author supplied metadata (automated record created 2010-03-12 12:08:51). Electronic resource. |
| Physical Description: | 1 online resource. |
| Bibliography: | Includes bibliographical references. |