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PIAS3, a member of the protein inhibitor of activated STAT family, was found to interact in vivo and in vitro with TIF2, a previously described coactivator for nuclear receptors. The interaction is mediated by two distinct non-contiguous regions of TIF2. We found that TIF2-PIAS3 interaction occurs through a unique domain of PIAS3, very rich in acidic residues and conserved throughout the PIAS family. PIAS3 modulates the ability of TIF2 to mediate ligand-enhanced transcription activation positively or negatively, for different steroid receptors. Taken together, our results indicate a potential role of PIAS3 as transcriptional modulator of TIF2-mediated signalling.

A mouse cDNA that encodes a nuclear DNA binding protein was identified by yeast two-hybrid screening using the activation domain 2 of the nuclear receptor coactivator TIF2 as a bait. BLAST analysis revealed that the identified cDNA encodes a KDWK domain and contains sequences almost identical to three tryptic peptides of rat GMEB-1 which together with the GMEB-2 heterodimeric partner binds to the GME/CRE sequence (glucocorticoid modulatory element) of the tyrosine aminotransferase (TAT) promoter. Mouse GMEB-1 is ubiquitously expressed in all the tissues examined. In vitro translated mGMEB-1 bound specifically to GME oligonucleotides, either alone or as a heterodimer with rGMEB-2. Transient transfection experiments with TAT promoter reporter genes suggest a potential role for mGMEB-1 as a transcriptional regulator of the TAT promoter.