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CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin–proteasome
Author(s) -
Zhang PeiJing,
Zhao Jie,
Li HuiYan,
Man JiangHong,
He Kun,
Zhou Tao,
Pan Xin,
Li AiLing,
Gong WeiLi,
Jin BaoFeng,
Xia Qing,
Yu Ming,
Shen BeiFen,
Zhang XueMin
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601602
Subject(s) - beijing , china , chinese academy of sciences , library science , center (category theory) , basic research , zhàng , political science , chemistry , computer science , law , crystallography
Accumulated evidence indicates that progesterone receptors (PR) are involved in proliferation of breast cancer cells and are implicated in the development of breast cancer. In this paper, a yeast two‐hybrid screen for PR led to the identification of CUE domain containing 2 (CUEDC2), whose function is unknown. Our results demonstrate that CUEDC2 interacts with PR and promotes progesterone‐induced PR degradation by the ubiquitin–proteasome pathway. The inhibition of endogenous CUEDC2 by siRNA nearly abrogated the progesterone‐induced degradation of PR, suggesting that CUEDC2 is involved in progesterone‐induced PR ubiquitination and degradation. Moreover, we identify the sumoylation site Lys‐388 of PR as the target of CUEDC2‐promoted ubiquitination. CUEDC2 decreases the sumoylation while promoting ubiquitination on Lys‐388 of PRB. We also show that CUEDC2 represses PR transactivation, inhibits the ability of PR to stimulate rapid MAPK activity, and impairs the effect of progesterone on breast cancer cell growth. Therefore, our results identify a key post‐translational mechanism that controls PR protein levels and for the first time provide an important insight into the function of CUEDC2 in breast cancer proliferation.