Estrogen receptor activation function 2 (AF-2) is essential for hormone-dependent transactivation and cell transformation induced by a v-Jun DNA binding domain-estrogen receptor chimera

Dunn, C.A., Clark, W., Black, E.J. and Gillespie, D.A.F. (2003) Estrogen receptor activation function 2 (AF-2) is essential for hormone-dependent transactivation and cell transformation induced by a v-Jun DNA binding domain-estrogen receptor chimera. Biochimica et Biophysica Acta: Gene Structure and Expression, 1628(3), pp. 147-155. (doi: 10.1016/S0167-4781(03)00136-2)

Full text not currently available from Enlighten.

Abstract

A chimeric protein consisting of the estrogen receptor alpha ligand binding domain (ER-alpha LBD) fused to the DNA binding domain (DBD) of the v-Jun oncoprotein, DeltavJ-hER, was previously shown to elicit estradiol-dependent transcriptional activation and cell trans fort-nation. Remarkably, in the unliganded state DeltavJ-hER is not inert, but rather inhibits cell proliferation. To understand the molecular basis for these opposite effects on cell growth, we investigated the effect of estradiol on DeltavJ-hER function. We find that DeltavJ-hER is localised to the cell nucleus and capable of binding TPA-response element (TRE) DNA recognition sites in the presence and absence of estradiol, indicating that these properties are unlikely to be the targets of hormonal regulation. In contrast, a mutant derivative of DeltavJ-hER in which amino acid substitutions selectively disrupt activation function 2 (AF-2) function is unable to elicit estradiol-dependent transcription or cell transformation, even though DNA binding is not impaired. Taken together, these observations establish that estrogen receptor AF-2 activity is essential for cell transformation by DeltavJ-hER.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Gillespie, Professor David
Authors: Dunn, C.A., Clark, W., Black, E.J., and Gillespie, D.A.F.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Biochimica et Biophysica Acta: Gene Structure and Expression
ISSN:0167-4781

University Staff: Request a correction | Enlighten Editors: Update this record