Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer.
Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer.
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靶向乳腺癌和前列腺癌中泛素化和降解的类固醇激素受体。
DOI：
10.1038/onc.2008.320
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发表时间：
2008-12-04
期刊：
影响因子：
8
通讯作者：
Sakamoto KM
中科院分区：
文献类型：
--
作者：
Rodriguez-Gonzalez A;Cyrus K;Salcius M;Kim K;Crews CM;Deshaies RJ;Sakamoto KM
Proteolysis targeting chimeric molecules (Protacs) target proteins for destruction by exploiting the ubiquitin-dependent proteolytic system of eukaryotic cells.We designed two Protacs that contain the peptide ‘degron’ from hypoxia-inducible factor-1α, which binds to the Von –Hippel–Lindau (VHL) E3 ubiquitin ligase complex, linked to either dihydroxytestosterone that targets the androgen receptor (AR; Protac-A), or linked to estradiol (E2) that targets the estrogen receptor-α (ERα; Protac-B). We hypothesized that these Protacs would recruit hormone receptors to the VHL E3 ligase complex, resulting in the degradation of receptors, and decreased proliferation of hormone-dependent cell lines. Treatment of estrogen-dependent breast cancer cells with Protac-B induced the degradation of ERα in a proteasome-dependent manner. Protac-B inhibited the proliferation of ERα-dependent breast cancer cells by inducing G1 arrest, inhibition of retinoblastoma phosphorylation and decreasing expression of cyclin D1, progesterone receptors A and B. Protac-B treatment did not affect the proliferation of estrogen-independent breast cancer cells that lacked ERα expression. Similarly, Protac-A treatment of androgendependent prostate cancer cells induced G1 arrest but did not affect cells that do not express AR. Our results suggest that Protacs specifically inhibit the proliferation of hormone-dependent breast and prostate cancer cells through degradation of the ERα and AR, respectively.
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影响因子：
5.2
作者：
Kirschberg, TA;VanDeusen, CL;Wender, PA
通讯作者：
Wender, PA
影响因子：
14.9
作者：
KLEINHITPASS, L;RYFFEL, GU;CATO, ACB
通讯作者：
CATO, ACB
影响因子：
82.9
作者：
Craft, N;Shostak, Y;Sawyers, CL
通讯作者：
Sawyers, CL
影响因子：
4.8
作者：
Alarid, ET;Preisler-Mashek, MT;Solodin, NM
通讯作者：
Solodin, NM
影响因子：
11.2
作者：
Duong, Vanessa;Boulle, Nathalie;Cavailles, Vincent
通讯作者：
Cavailles, Vincent