Cross‐inhibition of both estrogen receptor α and β pathways by each dominant negative mutant

FEBS Letters

Orimo, Akira¹  Inoue, Satoshi¹  Muramatsu, Masami¹  Ogawa, Sumito¹  Ouchi, Yasuyoshi²  Hosoi, Takayuki² 

[1] Department of Biochemistry, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-04, Japan;Department of Geriatrics, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan

关键词: Estrogen;    Estrogen receptor;    Heterodimer;    Transactivation;    Human;    ER;    estrogen receptor;    ERE;    estrogen response element;    RT-PCR;    reverse transcription polymerase chain reaction;    UTR;    untranslated region;    CAT;    chloramphenicol acetyltransferase;    GST;    glutathione S-transferase;    AF-2;    activation function 2;   

DOI  :  10.1016/S0014-5793(98)00079-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Both estrogen receptor α (ERα) and the recently identified ERβ are nuclear receptors that are activated by estrogen. It was reported that ERα and ERβ form heterodimers. Here, we show that they activate transcription independently rather than synergistically via estrogen response elements (ERE). To show the cross-talk between ERα and ERβ, we utilized dominant negative mutants of ERs constructed by C-terminal truncation. Interestingly, ERα1–530 inhibited transactivation not only by ERα but also by ERβ, whereas ERβ1–481 inhibited transactivation by ERα as well as by ERβ. The GST pull-down assay also demonstrated the cross-interaction of these mutants with wild-type ERα and ERβ. Thus, we found dominant negative mutants that block both ERα and ERβ signaling pathways.

【 授权许可】

Unknown