A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library

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.