Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain.
Transcription factors are often regulated by associated protein cofactors that are able to modify their activity by several different mechanisms. In this study we show that calreticulin, a Ca2+-binding protein with chaperone activity, binds to thyroid transcription factor-1 (TTF-1), a homeodomain-containing protein implicated in the differentiation of lung and thyroid. The interaction between calreticulin and TTF-1 appears to have functional significance because it results in increased transcriptional stimulation of TTF-1-dependent promoters. Calreticulin binds to the TTF-1 homeodomain and promotes its folding, suggesting that the mechanism involved in stimulation of transcriptional activity is an increase of the steady-state concentration of active TTF-1 protein in the cell. We also demonstrate that calreticulin mRNA levels in thyroid cells are under strict control by the thyroid-stimulating hormone, thus implicating calreticulin in the modulation of thyroid gene expression by thyroid-stimulating hormone.
Perrone
L
L
Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy.
Tell
G
G
Di Lauro
R
R
D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D037282:Calreticulin; D003001:Cloning, Molecular; D018076:DNA, Complementary; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D017510:Protein Folding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000074482:Thyroid Nuclear Factor 1; D013972:Thyrotropin / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*