TSG101 is thought as a putative tumor suppressor gene, and mutations of this gene were recently found in 7 of 15 breast cancer patients, though the physiological function remains to be elucidated. In this report, we showed that TSG101 protein acts as a transcriptional suppressor for estrogen receptor (ER) as well as other members of the nuclear hormone receptor super-family, VP16, and on its own. The basal promoter activity 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 protein did not have any histone acetylase nor deacetylase activity, which certain transcriptional co-factors have. The requirement of the same domain in the TSG101 protein for transcriptional suppression and in the tumor suppression indicates a possibility that transcriptional suppression of TSG101 is related to its tumor suppression.
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