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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

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 17?-estradiol
(E2) and transfected with a construct containing three tandem estrogen
responsive elements (pERE3), DRIP205 coactivates ER?-mediated
transactivation. DRIP205?587-636 is a DRIP205 mutant in which both NR boxes
within amino acids 587-636 have been deleted and, in parallel transfection
studies, DRIP205?587-636 also coactivates ER?. Moreover, both wild-type and
variant DRIP205 also colocalize with ER? in the nuclei of transfected cells. AF1
and AF2 of ER? are both required for DRIP205 coactivation. Extensive deletion
analysis of DRIP205 shows that multiple domains of this protein play a role in
coactivation of ER? and in interactions with ER?. On the other hand, both
DRIP205 and DRIP205?587-636 coactivate E2-induced transactivation of ER?/Sp1 in cells transfected with a construct containing three GC-rich sites
(pSp13). Coactivation of ER?/Sp1 by DRIP205 is dependent on AF1 of ER?.
Enhancement of ER? and ER?/Sp1 by DRIP205 does not require NR boxes of
DRIP205, and deletion mutants DRIP205 (1-714) and DRIP205 (516-1566)
significantly coactivate ER? and ER?/Sp1. RNA interference study showed that
DRIP205 coactivation of ER?/Sp was abolished in cells transfected with iSp3
and iSp4, suggesting that Sp3 and Sp4 are required for coactivation of ER?/Sp
by DRIP205 in ZR-75 cells.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-1008
Date15 May 2009
CreatorsWu, Qian
ContributorsSafe, Stephen
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
TypeBook, Thesis, Electronic Dissertation, text
Formatelectronic, application/pdf, born digital

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