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 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.
Watanabe
M
M
Institute of Molecular and Cellular Biosciences, Faculty of Medicine, University of Tokyo, Japan.
Yanagi
Y
Y
Masuhiro
Y
Y
Yano
T
T
Yoshikawa
H
H
Yanagisawa
J
J
Kato
S
S
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D016350:Leucine Zippers; D011487:Protein Conformation; D011960:Receptors, Estrogen / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D015533:Transcriptional Activation; D000099177:Tsg101 Protein
D000123:Acetyltransferases; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D017405:Herpes Simplex Virus Protein Vmw65; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D011960:Receptors, Estrogen; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000099177:Tsg101 Protein