The type II transforming growth factor (TGF)-beta receptor-interacting protein TRIP-1 acts as a modulator of the TGF-beta response.

The transforming growth factor-beta (TGF-beta) receptor interacting protein TRIP-1 was originally identified as a WD40 repeat-containing protein that has the ability to associate with the TGF-beta type II receptor and is phosphorylated by it (1). However, its function was not known. We now show that TRIP-1 expression represses the ability ...
of TGF-beta to induce transcription from the plasminogen activator inhibitor-1 promoter, a common reporter of the TGF-beta-induced gene expression response, but does not affect the ability of TGF-beta to inhibit cyclin A transcription. TRIP-1 can also inhibit the plasminogen activator inhibitor-1 expression induced by Smads as well as activated TGF-beta type I receptors. Its inhibitory effect is exerted by a combination of receptor-dependent and receptor-independent mechanisms. Deletion mutational analysis revealed that two distinct regions, which do not contain recognizable WD40 repeats, are required for the ability of TRIP-1 to inhibit the gene expression response. Expression of other segments of TRIP-1 increased the TGF-beta-induced gene expression response and therefore may exert a dominant negative phenotype. We conclude that TRIP-1 acts as a modulator of the TGF-beta response.
Mesh Terms:
Binding Sites, Cyclin A, DNA Mutational Analysis, DNA-Binding Proteins, Eukaryotic Initiation Factor-3, Gene Expression Regulation, Humans, Plasminogen Activator Inhibitor 1, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Proteins, Receptors, Transforming Growth Factor beta, Sequence Deletion, Signal Transduction, Smad3 Protein, Smad4 Protein, Trans-Activators, Transcription, Genetic, Transforming Growth Factor beta
J. Biol. Chem.
Date: Nov. 20, 1998
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