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Cancer Promoted by the Oncoprotein v-ErbA May Be Due to Subcellular Mislocalization of Nuclear Receptors
Bonamy, Ghislain M.C. Guiochon-Mantel, Anne Allison, Lizabeth A.
Bonamy, Ghislain M.C.
Guiochon-Mantel, Anne
Allison, Lizabeth A.
Abstract
The retroviral v-ErbA oncoprotein is a highly mutated variant of the thyroid hormone receptor α (TRα), which is unable to bind T3 and interferes with the action of TRα in mammalian and avian cancer cells. v-ErbA dominant-negative activity is attributed to competition with TRα for T3-responsive DNA elements and/or auxiliary factors involved in the transcriptional regulation of T3-responsive genes. However, competition models do not address the altered subcellular localization of v-ErbA and its possible implications in oncogenesis. Here, we report that v-ErbA dimerizes with TRα and the retinoid X receptor and sequesters a significant fraction of the two nuclear receptors in the cytoplasm. Recruitment of TRα to the cytoplasm by v-ErbA can be partially reversed in the presence of ligand and when chromatin is disrupted by the histone deacetylase inhibitor trichostatin A. These results define a new mode of action of v-ErbA and illustrate the importance of cellular compartmentalization in transcriptional regulation and oncogenesis.
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2005-05-01
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Biology
DOI
https://doi.org/10.1210/me.2004-0204