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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 17 - 27 (11page)
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Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors.However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes byUSP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.
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참고문헌 (40)
참고문헌 신청
Cao, Q. / 2008 / Repression of E-cadherin by the polycomb group protein EZH2 in cancer / Oncogene 27:7274~7284
Chen, H. / 2005 / Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2complex and histone deacetylase in prostate cancer / J. Biol. Chem 280:22437~22444
Chen, Y. / 2017 / USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma / Onco. Targets Ther 10:681~689
de Bie, P. / 2010 / Regulation of the Polycomb protein RING1B ubiquitination by USP7 / Biochem. Biophys. Res. Commun 400:389~395
Fuchs, G. / 2012 / RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation / Mol. Cell 46:662~673
Chen, H. / 2005 / Down-regulation of human DAB2IP gene expression mediated by polycomb Ezh2complex and histone deacetylase in prostate cancer / J. Biol. Chem 280:22437~22444
Chen, Y. / 2017 / USP21 promotes cell proliferation and metastasis through suppressing EZH2 ubiquitination in bladder carcinoma / Onco. Targets Ther 10:681~689
de Bie, P. / 2010 / Regulation of the Polycomb protein RING1B ubiquitination by USP7 / Biochem. Biophys. Res. Commun 400:389~395
Fuchs, G. / 2012 / RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation / Mol. Cell 46:662~673
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