Physical and functional interactions between Daxx and TSG101.

Daxx has been reported to mediate the Fas/JNK-dependent signals in the cytoplasm. However, several evidences have suggested that Daxx is located mainly in the nucleus and functions as a transcriptional regulator. Recently, we identified DMAP1, a TSG101-interacting protein as a Daxx binding partner by yeast two-hybrid screening. TSG101 has been shown to act as transcriptional co-repressor of nuclear hormone receptors. Here we examined whether TSG101also interacts with Daxx directly. The association of Daxx and TSG101 was confirmed using co-expressed tagged proteins. The interaction regions in both proteins were also mapped, and the cellular localization of the interaction was examined. TSG101 formed a complex with Daxx through its coiled-coil domain and co-localized in the nucleus. Furthermore, TSG101 enhanced Daxx-mediated repression of glucocorticoid receptor transcriptional activity. These results provide the novel molecular interactions between Daxx and TSG101, which establish an efficient repressive transcription complex in the nucleus.