Proteasome-mediated mineralocorticoid receptor degradation attenuates transcriptional response to aldosterone

Kenichi Yokota, Hirotaka Shibata, Sakiko Kobayashi, Noriko Suda, Ayano Murai, Isao Kurihara, Ikuo Saito, Takao Saruta

研究成果: Article査読

21 被引用数 (Scopus)


The ubiquitin-proteasome pathway regulates the turnover of many nuclear hormone receptors, such as the estrogen receptor. For estrogen receptor, proteasome inhibition decreases ligand-mediated transcription. We provide evidence that the mineralocorticoid receptor (MR) is degraded by the ubiquitin-proteasome pathway in a ligand-dependent manner and that proteasomal inhibition results in increased accumulation of the MR with enhancement of transcriptional response to aldosterone. Examination of the primary sequence of human and rat MR has identified two candidate PEST degradation motifs. Mutation of lysine 715 and/or 367 within this PEST element failed to prevent degradation of MR protein or transcriptional activity mediated by aldosterone, indicating that other lysine residues are targeted by proteasomal degradation of MR. These findings demonstrate a coupling between MR up-regulation and transcriptional hyperactivity.

ジャーナルEndocrine Research
出版ステータスPublished - 2004 12 1

ASJC Scopus subject areas

  • Endocrinology

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