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Mapping and Functional Role of Phosphorylation Sites in the Thyroid Transcription Factor-1 (TTF-1)

Zannini, Mariastella and Acebron, Alvaro and De Felice, Mario and Arnone, Maria Ina and Martin-Pérez, Jorge and Santisteban, Pilar and Di Lauro, Roberto (1996) Mapping and Functional Role of Phosphorylation Sites in the Thyroid Transcription Factor-1 (TTF-1). Journal of Biological Chemistry, 271 (4). pp. 2249-2254. ISSN 0021-9258.

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The phosphorylation of thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase gene promoters, has been studied. Phosphorylation occurs on a maximum of seven serine residues that are distributed in three tryptic peptides. Mutant derivatives of TTF-1, with alanine residues replacing the serines in the phosphorylation sites, have been constructed and used to assess the functional relevance of TTF-1 phosphorylation. The DNA binding activity of TTF-1 appears to be phosphorylation-independent, as indicated also by the performance of TTF-1 purified from an overexpressing Escherichia coli strain. Transcriptional activation by TTF-1 could require phosphorylation only in specific cell types since in a co-transfection assay in heterologous cells both wild-type and mutant proteins show a similar transcriptional activity.

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Additional Information:©1996 by The American Society for Biochemistry and Molecular Biology, Inc. (Received for publication, August 14, 1995, and in revised form, October 12, 1995) This work was supported by grants from the Progetto Finalizzato Applicazioni Cliniche della Ricerca Oncologica of Consiglio Nazionale delle Ricerche, the Associazione Italiana per la Ricerca sul Cancro, the Commission of the European Communities (BIO2 CT 930454), and Grants DGYCIT (PB94-0092, PB93-0136), and CAM (C263/91A, AE00310/95) from the Fundación Ramón Areces. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Record Number:CaltechAUTHORS:ZANjbc96
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ID Code:10831
Deposited By: Archive Administrator
Deposited On:12 Jun 2008
Last Modified:03 Oct 2019 00:13

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