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A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library
1Cancer Research Center, La Jolla Cancer Research Foundation, CA 92037.
Abstract:
The c-erbA gene belongs to a multigene family that encodes transcriptional regulatory proteins including the v-erbA oncogene product, steroid hormone receptors, and the vitamin D3 receptor. A v-erbA DNA probe encoding the DNA-binding region of the v-erbA protein was used to screen a human complementary DNA testis library. One of the clones isolated, erbA-T-1, was found to encode a 490-amino acid protein (erbA-T). The erbA-T polypeptide shows high homology with the proteins encoded by both the chicken c-erbA and the human c-erbA-beta genes but is most closely related to the chicken gene. The chicken c-erbA and the human c-erbA-beta genes encode high-affinity receptors for thyroid hormone, and here it is shown that the erbA-T protein binds specifically to 3,5,3'-triiodo-L-thyronine with a dissociation constant of 3.8 +/- 0.2 x 10(-10) M. These data imply that more than one thyroid hormone receptor exists in humans and that these receptors might have different tissue- and gene-activating specificities.
Insights
Researchers identified a novel human thyroid hormone receptor, erbA-T, by screening a testis cDNA library. This discovery suggests multiple human thyroid hormone receptors with distinct tissue and gene-activating specificities exist.
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- The c-erbA gene family encodes transcriptional regulators, including steroid hormone and vitamin D3 receptors.
- The v-erbA oncogene product is also part of this multigene family.
- Thyroid hormone receptors are crucial for regulating gene expression.
Purpose of the Study:
- To identify novel human genes related to the c-erbA family.
- To characterize a newly isolated human gene product for its potential role as a thyroid hormone receptor.
- To investigate the existence of multiple thyroid hormone receptors in humans.
Main Methods:
- Screening of a human complementary DNA (cDNA) testis library using a v-erbA DNA probe.
- Isolation and sequencing of a specific clone, erbA-T-1.
- Analysis of the encoded protein's (erbA-T) homology with known c-erbA proteins.
- Binding assays to determine the interaction of erbA-T with 3,5,3'-triiodo-L-thyronine (T3).
Main Results:
- A novel human cDNA clone, erbA-T-1, encoding a 490-amino acid protein (erbA-T) was isolated.
- The erbA-T protein exhibits high homology to chicken c-erbA and human c-erbA-beta proteins.
- erbA-T specifically binds 3,5,3'-triiodo-L-thyronine (T3) with a high affinity (Kd = 3.8 +/- 0.2 x 10(-10) M).
Conclusions:
- The data indicate the existence of at least one additional thyroid hormone receptor in humans, designated erbA-T.
- This novel receptor may possess distinct tissue-specific and gene-activating functions compared to other known thyroid hormone receptors.
- The findings suggest a more complex regulatory network for thyroid hormone action in humans.