Implication of proteasome in estrogen receptor degradation

FEBS Letters

El Khissiin, Abdelhamid¹  Leclercq, Guy¹ 

[1] Laboratoire J.C. Heuson de Cancérologie Mammaire, Service de Médecine, Institut Jules Bordet, 1. rue Héger-Bordet, 1000 Brussels, Belgium

关键词: Proteasome;    Lysosome;    Calpain;    Estrogen receptor;    MCF-7 cell;   

DOI  :  10.1016/S0014-5793(99)00343-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In MCF-7 breast cancer cells, estradiol (E₂) and pure antiestrogen RU 58668 down-regulate the estrogen receptor (ER). Interestingly, the protein synthesis inhibitor cycloheximide (CHX) abrogated solely the effect of E₂ suggesting a selective difference in the degradation of the receptor induced by estrogenic and antiestrogenic stimulations. A panel of lysosome inhibitors (i.e. bafilomycin, chloroquine, NH₄Cl, and monensin), calpain inhibitors (calpastatin and PD 150606) and proteasome inhibitors (lactacystin and proteasome inhibitor I) were tested to assess this hypothesis. Among all inhibitors tested, lactacystin and proteasome inhibitor I were the sole inhibitors to abrogate the elimination of the receptor induced by both E₂ and RU 58668; this selective effect was also recorded in cells prelabeled with [³H]tamoxifen aziridine before exposure to these ligands. Hence, differential sensitivity to CHX seems to be linked to the different mechanisms which target proteins for proteasome-mediated destruction. Moreover, the two tested proteasome inhibitors produced a slight increase of ER concentration in cells not exposed to any ligand, suggesting also the involvement of proteasome in receptor turnover.

【 授权许可】

Unknown