Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein.
Thyroid hormone receptors (TRs) are members of the steroid hormone/retinoic acid receptor superfamily, which regulate homeostasis, development, and differentiation. Their transcriptional activity is modulated by the thyroid hormone 3,3',5-triiodo-L-thyronine (T3). The present study evaluated the effect of the availability of cytoplasmic T3 on the modulation of transcriptional responses of the TRs. In human choriocarcinoma JEG-3 and monkey COS-1 cells, the cytosolic thyroid hormone binding protein is a monomer of the tetrameric pyruvate kinase, subtype M2, which does not bind T3. The in vivo monomer-tetramer interconversion is regulated by glucose via fructose 1,6-bisphosphate. At the physiological T3 concentration, lowering the glucose concentration led to an increase in the cellular concentration of the cytosolic thyroid hormone binding protein. By using a transient transfection system, a concomitant reduction in the transcriptional activity of the human beta 1 thyroid hormone receptor was detected in both cell lines. In the absence of glucose, the transcriptional activity of the human beta 1 thyroid hormone receptor in JEG-3 and COS-1 cells was reduced by 65-75% and 90-95%, respectively. However, glucose had no effect on the basal transcriptional activity. These findings demonstrate an important prenuclear step in the modulation of the gene regulating activity of the TRs.
Ashizawa
K
K
Gene Regulation Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Cheng
S Y
SY
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002822:Choriocarcinoma; D003600:Cytosol / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000494:pharmacology; D000882:Haplorhini; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000378:metabolism*; D011247:Pregnancy; D011770:Pyruvate Kinase / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D002352:Carrier Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D015500:Chloramphenicol O-Acetyltransferase; D011770:Pyruvate Kinase; D005947:Glucose