Fatty acyl-CoA binding activity of the nuclear thyroid hormone receptor.
Long-chain fatty acids and their acyl-CoA esters are potent inhibitors of nuclear thyroid hormone (T3) receptor in vitro. In the present study, we obtained evidence for acyl-CoA binding activity in the nuclear extract from rat liver. The activity sedimented at a position (3.5 S) identical with that of the T3 receptor, and the two activities sedimented together. Similarly, they coeluted on DEAE-Sephadex. After partial purification of the receptor, it was again inhibited strongly by acyl-CoAs. Heat stability and a partial trypsin digestion of the receptor both suggested that the action site of oleoyl-CoA overlapped the T3-binding domain of the receptor. In addition, thyroid hormone receptor beta 1, synthesized in vitro, bound oleoyl-CoA specifically and its T3-binding activity was inhibited. The dissociation constant for oleoyl-CoA binding to the partially purified receptor was 1.2 x 10(-7) M. This value as well as its molecular size distinguished the nuclear binding sites from the cytoplasmic fatty acid/acyl-CoA binding proteins. Oleoyl-CoA had no effect on the glucocorticoid receptor, another member of the nuclear hormone-receptor superfamily. From these results, we propose that thyroid hormone receptor is a specific acyl-CoA binding protein of the cell nucleus.
Department of Biochemistry, Osaka City University Medical School, Japan.
Q
Q
Li
N
N
Yamamoto
S
S
Morisawa
A
A
Inoue
D000214:Acyl Coenzyme A / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry*; D003907:Dexamethasone / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000737:chemistry; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000302:isolation & purification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D000214:Acyl Coenzyme A; D005227:Fatty Acids; D009829:Oleic Acids; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; C028697:dexamethasone receptor; D014284:Triiodothyronine; C017585:oleoyl-coenzyme A; D019301:Oleic Acid; D003907:Dexamethasone