TY - JOUR
T1 - Differential requirements of Hsp90 and DNA for the formation of estrogen receptor homodimers and heterodimers
AU - Powell, Emily
AU - Wang, Yidan
AU - Shapiro, David J.
AU - Xu, Wei
PY - 2010/5/21
Y1 - 2010/5/21
N2 - The two estrogen receptor (ER) subforms, ERα and ERβ, are capable of forming DNA-binding homodimers and heterodimers. Although binding to DNA is thought to stabilize ER dimers, how ERα/α, ERβ/β, and ERα/β dimerization is regulated by DNA and the chaperone protein Hsp90 is poorly understood. Using our highly optimized bioluminescence resonance energy transfer assays in conjunction with assays for transcriptional activation of ERs, we determined that DNA binding appears to play a minor role in the stabilization of ER dimers, especially in the case of ERβ/β homodimers. These findings suggest that ER dimers form before they associate with chromatin and that DNA binding plays a minor role in stabilizing ER dimers. Additionally, although Hsp90 is essential for the proper dimerization of ERα/α and ERα/β, it is not required for the proper dimerization of ERβ/β. Despite this, Hsp90 is critical for the estrogen-dependent transcriptional activity of the ERβ/β homodimer. Thus, Hsp90 is implicated as an important regulator of distinct aspects of ERα and ERβ action.
AB - The two estrogen receptor (ER) subforms, ERα and ERβ, are capable of forming DNA-binding homodimers and heterodimers. Although binding to DNA is thought to stabilize ER dimers, how ERα/α, ERβ/β, and ERα/β dimerization is regulated by DNA and the chaperone protein Hsp90 is poorly understood. Using our highly optimized bioluminescence resonance energy transfer assays in conjunction with assays for transcriptional activation of ERs, we determined that DNA binding appears to play a minor role in the stabilization of ER dimers, especially in the case of ERβ/β homodimers. These findings suggest that ER dimers form before they associate with chromatin and that DNA binding plays a minor role in stabilizing ER dimers. Additionally, although Hsp90 is essential for the proper dimerization of ERα/α and ERα/β, it is not required for the proper dimerization of ERβ/β. Despite this, Hsp90 is critical for the estrogen-dependent transcriptional activity of the ERβ/β homodimer. Thus, Hsp90 is implicated as an important regulator of distinct aspects of ERα and ERβ action.
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U2 - 10.1074/jbc.M110.104356
DO - 10.1074/jbc.M110.104356
M3 - Article
C2 - 20353944
AN - SCOPUS:77952369277
SN - 0021-9258
VL - 285
SP - 16125
EP - 16134
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 21
ER -