Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer Article

Rodriguez-Gonzalez, A, Cyrus, K, Salcius, M et al. (2008). Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer . ONCOGENE, 27(57), 7201-7211. 10.1038/onc.2008.320

cited authors

  • 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 androgen-dependent 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. © 2008 Macmillan Publishers Limited All rights reserved.

publication date

  • December 4, 2008

published in

Digital Object Identifier (DOI)

start page

  • 7201

end page

  • 7211


  • 27


  • 57