A PUTATIVE TUMOR-SUPPRESSOR, TSG101, ACTS AS A TRANSCRIPTIONAL SUPPRESSOR THROUGH ITS COILED-COIL DOMAIN

TSG101 is thought as a putative tumor suppressor gene, and mutations o f this gene were recently found in 7 of 15 breast cancer patients, tho ugh the physiological function remains to be elucidated. In this repor t, we showed that TSG101 protein acts as a transcriptional suppressor for estrogen receptor (ER) as well as other members of the nuclear hor mone receptor superfamily, VP16, and on its own. The basal promoter ac tivity was also inhibited by TSG101. The suppression of transcription by TSG101 protein required its coiled-coil domain, which is also shown to be required for the tumor suppressive function. Expressed TSG101 p rotein did not have any histone acetylase nor deacetylase activity, wh ich certain transcriptional co-factors have. The requirement of the sa me domain in the TSG101 protein for transcriptional suppression and in the tumor suppression indicates a possibility that transcriptional su ppression of TSC101 is related to its tumor suppression. (C) 1998 Acad emic Press.