An AP-1-like factor and the pituitary-specific factor Pit-1 are both necessary to mediate hormonal induction of human thyrotropin β gene expression

Myung K. Kim, John H. McClaskey, Donald L. Bodenner, Bruce D. Weintraub

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

The human thyrotropin β (hTSHβ) gene is inducible by various agents including thyrotropin-releasing hormone, phorbol esters, or the adenylyl cyclase activator forskolin. In this study, we have characterized the functional properties of the TGGGTCA motif at -1/+6 of the hTSHβ gene that is similar to the consensus phorbol ester response element (TRE) or the consensus cyclic AMP response element (CRE). We suggest that both protein kinases C and A as well as TRH share a common mediator which recognizes the TGGGTCA element in activating the hTSHβ promoter. Following stimulation by phorbol esters, forskolin, or TRH, the TGGGTCA-specific factor acts together with the pituitary-specific transcription factor Pit-1 (or GHF-1) bound to upstream sequences at -128 to -61 to mediate the induction of the hTSHβ promoter. The induction requires that both factors bind to their own binding sites, but Pit-1 neither increases the binding of the TGGGTCA-specific factor to its target sequences nor associates with this factor to form a heterodimer. The TGGGTCA-specific factor is present in three cell lines tested and is composed of protein(s) immunologically related to c-Jun and c-Fos but not to the CRE-binding protein, CREB. By using the hTSHβ reporter plasmids in which the TGGGTCA element is converted to consensus TRE or CRE motifs, we found that, within the context of the hTSHβ promoter, the TGGGTCA element is a more potent TRE or CRE than the consensus TRE or CRE sequences. Based upon the results of this study, we propose a model in which the TGGGTCA-specific AP-1-like factor functionally cooperates with the tissue-specific factor Pit-1 to activate the hTSHβ gene.

Original languageEnglish
Pages (from-to)23366-23375
Number of pages10
JournalJournal of Biological Chemistry
Volume268
Issue number31
StatePublished - 5 Nov 1993
Externally publishedYes

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