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Differences in the Abilities of Estrogen Receptors to Integrate Activation Functions Are Critical for Subtype-Specific Transcriptional Responses

Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Mesut Muyan, Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642. E-mail: mesut_muyan{at}urmc.rochester.edu.

Estrogen receptors (ER) and ß are members of a superfamily of nuclear receptors and mediate estrogen [17ß-estradiol (E2)] signaling. ERß has considerably less transcription potency than ER in heterologous expression systems that use E2 response elements (ERE) in tandem as the trans-acting unit. We show here that despite similar intracellular characteristics, ERß, in contrast to ER, fails to induce gene transcription synergistically in response to E2 from tandem EREs. Moreover, our results indicate that ER-specific partial agonistic activity of antagonists occurs additively. Although synergy contributes, it is not sufficient for differences in the transcription potencies between the ER subtypes. We demonstrate here that differences in the abilities of ERs to integrate activation functions through functional interactions between amino and carboxyl termini are critical for the transcriptional strength of ER subtypes.

NURSA Molecule Pages Link:

Nuclear Receptors:   ERα  |  ERβ

Coregulators:   GRIP1

Ligands:   17β-Estradiol  |  4-Hydroxytamoxifen

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