Organismic functions of Trip6

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Trip6 has been isolated in our laboratory as a glucocorticoid receptor (GR) interacting protein. It carries three LIM domains in its C-terminal half, each one of which defines different interaction specificities. N-terminal to the LIM domains Trip6 carries a dimerization sequence. By an alternative translational start site which eliminates a nuclear export sequence, but not the dimerization domain, a nuclear form, nTrip6, is formed. The homodimeric nTrip6 binds to promoter-associated transcription factors such as GR, Fos:Jun and p65-NF-(B, and stimulates transcription. Due to its several interaction domains nTrip6 can assemble additional transcription factors on top of the DNA-bound factor. This converts the complex most frequently into a repressing mode, e.g. when assembling a nuclear hormone receptor on top of Fos:Jun or NF-(B. By this action activated GR inhibits inflammatory processes. The other alternative 3 translational product is exported from the nucleus and is associated with the plasma membrane at focal adhesions. It also homodimerizes, interacts with several other proteins of the focal adhesion complex and appears to be regulated by phosphorylation of an N-terminal site. Both forms thus exhibit distinct functions: transcriptional regulation by nTrip6, membrane-associated functions such as migration, adhesion and possibly tumorigenesis (see later) by the long form.