Section 11
Chapter 10,608

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.; Gillespie, D.A.F.

Biochimica et Biophysica Acta 1628(3): 147-155


ISSN/ISBN: 0006-3002
PMID: 12932827
DOI: 10.1016/s0167-4781(03)00136-2
Accession: 010607793

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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 transformation. 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.

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