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.
Bonamy, Ghislain M.C.; Guiochon-Mantel, Anne; and Allison, Lizabeth A., Cancer Promoted by the Oncoprotein v-ErbA May Be Due to Subcellular Mislocalization of Nuclear Receptors (2005). Molecular Endocrinology, 19(5), 1213-1230.
A correction has been published: Molecular Endocrinology, Volume 19, Issue 8, 1 August 2005, Page 2085, https://doi.org/10.1210/mend.19.8.9999