Mol. Cells 2019; 42(): 1081  https://doi.org/10.14348/molcells.2018.0329
USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
Jae Min Park1, Jae Eun Lee1, Chan Mi Park1, and Jung Hwa Kim1,*
1Department of Biological Sciences, Inha University, Incheon 22212, Korea
*Correspondence: jhkim4@inha.ac.kr
Received August 2, 2018; Revised September 18, 2018; Accepted October 11, 2019.; Published online January 2, 2019.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
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.
Keywords:
EZH2, prostate cancer cells, protein stability, USP44


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31 December 2018 Volume 41,
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