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Research Article

Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

A Riccio, P V Pedone, L R Lund, T Olesen, H S Olsen, P A Andreasen
A Riccio
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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P V Pedone
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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L R Lund
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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T Olesen
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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H S Olsen
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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P A Andreasen
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, University of Naples, Italy.
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DOI: 10.1128/MCB.12.4.1846
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ABSTRACT

Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action.

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Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.
A Riccio, P V Pedone, L R Lund, T Olesen, H S Olsen, P A Andreasen
Molecular and Cellular Biology Apr 1992, 12 (4) 1846-1855; DOI: 10.1128/MCB.12.4.1846

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Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.
A Riccio, P V Pedone, L R Lund, T Olesen, H S Olsen, P A Andreasen
Molecular and Cellular Biology Apr 1992, 12 (4) 1846-1855; DOI: 10.1128/MCB.12.4.1846
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