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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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Autores principales: Park, Jae Min, Lee, Jae Eun, Park, Chan Mi, Kim, Jung Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354053/
https://www.ncbi.nlm.nih.gov/pubmed/30622230
http://dx.doi.org/10.14348/molcells.2018.0329
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author Park, Jae Min
Lee, Jae Eun
Park, Chan Mi
Kim, Jung Hwa
author_facet Park, Jae Min
Lee, Jae Eun
Park, Chan Mi
Kim, Jung Hwa
author_sort Park, Jae Min
collection PubMed
description 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.
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spelling pubmed-63540532019-02-11 USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization Park, Jae Min Lee, Jae Eun Park, Chan Mi Kim, Jung Hwa Mol Cells Article 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. Korean Society for Molecular and Cellular Biology 2019-01-31 2019-01-02 /pmc/articles/PMC6354053/ /pubmed/30622230 http://dx.doi.org/10.14348/molcells.2018.0329 Text en © The 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/.
spellingShingle Article
Park, Jae Min
Lee, Jae Eun
Park, Chan Mi
Kim, Jung Hwa
USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title_full USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title_fullStr USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title_full_unstemmed USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title_short USP44 Promotes the Tumorigenesis of Prostate Cancer Cells through EZH2 Protein Stabilization
title_sort usp44 promotes the tumorigenesis of prostate cancer cells through ezh2 protein stabilization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354053/
https://www.ncbi.nlm.nih.gov/pubmed/30622230
http://dx.doi.org/10.14348/molcells.2018.0329
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