E1AF degradation by a ubiquitin-proteasome pathway.
E1AF is a member of the ETS family of transcription factors. In mammary tumors, overexpression of E1AF is associated with tumorigenesis, but E1AF protein has hardly been detected and its degradation mechanism is not yet clear. Here we show that E1AF protein is stabilized by treatment with the 26S protease inhibitor MG132. We found that E1AF was modified by ubiquitin through the C-terminal region and ubiquitinated E1AF aggregated in nuclear dots, and that the inhibition of proteasome-activated transcription from E1AF target promoters. These results suggest that E1AF is degraded via the ubiquitin-proteasome pathway, which has some effect on E1AF function.
Takahashi
Akiko
A
Department of Oral Pathobiological Science, Hokkaido University Graduate School of Dental Medicine, North 13 West 7, Kita-ku 060-8586, Sapporo, Japan.
Higashino
Fumihiro
F
Aoyagi
Mariko
M
Yoshida
Koichi
K
Itoh
Miyuki
M
Kobayashi
Masanobu
M
Totsuka
Yasunori
Y
Kohgo
Takao
T
Shindoh
Masanobu
M
D017500:Adenovirus E1A Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D022003:Cell Nucleus Structures / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; D007976:Leupeptins; D061988:Proteasome Inhibitors; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde