Comparison of the DNA binding specificity and function of v-ErbA and thyroid hormone receptor alpha 1.
The oncoprotein v-ErbA is a mutated version of thyroid hormone receptor alpha 1. Although the basis for the oncogenic action of v-ErbA is unknown, expression of this protein is known to inhibit thyroid hormone and retinoic acid induction of target genes. The DNA binding domain of v-ErbA differs from that of thyroid hormone receptor alpha 1 in two amino acids felt to be crucial for determining the specificity of DNA binding. However, the DNA binding properties of v-ErbA have not been examined independent of a comparison of binding to already known thyroid hormone response elements. In the current studies a non-biased strategy was used to select from a pool of random DNA those sequences that bind v-ErbA with high affinity. The highest affinity binding sequence was identified as the decamer 5'-T(A/G)AGGTCACG, which is closely related to the optimal thyroid hormone receptor alpha 1 binding sequence, TAAG-GTCA. Transfection studies demonstrate that among equal thyroid hormone responsive elements, those that contain the optimal v-ErbA consensus will be repressed by v-ErbA in preference to those that do not. These studies indicate that v-ErbA and thyroid hormone receptor alpha 1 regulate overlapping sets of response elements, and that all sequences that are highly responsive to thyroid hormone are not necessarily responsive to v-ErbA.
Subauste
J S
JS
Division of Endocrinology and Metabolism, University of Michigan Medical Center, Ann Arbor 48109-0678, USA.
Koenig
R J
RJ
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D008969:Molecular Sequence Data; D018774:Oncogene Proteins v-erbA / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014162:Transfection
D017931:DNA Primers; D018774:Oncogene Proteins v-erbA; D011988:Receptors, Thyroid Hormone; D004247:DNA