title: Calreticulin enhances the transcriptional activity of thyroid transcription factor-1 by binding to its homeodomain.
abstract: 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.
authors.affiliation: Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Perrone
authors.forename: G
authors.initials: G
authors.lastname: Tell
authors.forename: R
authors.initials: R
authors.lastname: Di Lauro
mesh_terms: 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*