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

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 ze...

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Bibliographic Details
Published in:Molecules and cells 2019, 42(1), , pp.17-27
Main Authors: Park, Jae Min, Lee, Jae Eun, Park, Chan Mi, Kim, Jung Hwa
Format: Article
Language:English
Subjects:
Carcinogenesis - metabolism
Carcinogenesis - pathology
Cell Line, Tumor
Enhancer of Zeste Homolog 2 Protein - metabolism
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HEK293 Cells
Humans
Male
Mutant Proteins - metabolism
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Protein Binding
Protein Stability
Ubiquitin Thiolesterase
Ubiquitin-Specific Proteases - metabolism
Ubiquitination
생물학
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Summary: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.
ISSN:1016-8478
0219-1032
DOI:10.14348/molcells.2018.0329