USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization

被引：42

作者：

Park, Jae Min ^{[1
]}

Lee, Jae Eun ^{[1
]}

Park, Chan Mi ^{[1
]}

Kim, Jung Hwa ^{[1
]}

机构：

[1] Inha Univ, Dept Biol Sci, Incheon 22212, South Korea

来源：

MOLECULES AND CELLS | 2019年 / 42卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

EZH2; prostate cancer cells; protein stability; USP44; TUMOR-SUPPRESSOR; GENE-EXPRESSION; HISTONE H3; E-CADHERIN; LYSINE; 27; POLYCOMB; UBIQUITINATION; REPRESSION; COMPLEX; TARGET;

D O I：

10.14348/molcells.2018.0329

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 by USP44 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.

引用

页码：17 / 27

页数：11

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