Identification and characterization of the AF-1 transactivation domain of thyroid hormone receptor beta1.
Physiological responses to thyroid hormones are regulated by a set of nuclear receptors (TRs) related to the steroid receptor superfamily of ligand-dependent transcription factors. Although TR isoforms are highly conserved in their DNA binding, ligand binding, and carboxyl-terminal transactivation domains, their amino-terminal regions are completely divergent. We examined the contribution of these amino-terminal sequences to TRbeta1 function. An amino-terminally truncated version of rat TRbeta1 lacking amino acids 4-89 was impaired in hormone-dependent activation in both yeast and mammalian cells. This defect was not due to impairment of DNA binding, because the truncated receptor displayed enhanced homodimer binding on several different TREs, indicating that residues in the amino-terminal domain of TRbeta1 interfere with homodimerization of the receptor. The presence of an autonomous transactivation domain in the amino-terminal region was demonstrated by its ability to activate transcription in a constitutive manner when fused to the GAL4 DNA binding domain. Deletional analyses localized the residues comprising the amino-terminal transactivation region of TRbeta1 to 19 amino acids residing between residues 69 and 89. Thus, the amino-terminal region of TRbeta1 contains an activation domain (AF-1) that can modulate the function of the receptor and may allow for the fine-tuning of receptor activity in various target tissues.
Wilkinson
J R
JR
Department of Biochemistry and Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Towle
H C
HC
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins