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Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis

Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this...

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Autores principales: Chandrasekaran, Arun Pandian, Woo, Sang Hyeon, Sarodaya, Neha, Rhie, Byung Ho, Tyagi, Apoorvi, Das, Soumyadip, Suresh, Bharathi, Ko, Na Re, Oh, Seung Jun, Kim, Kye-Seong, Ramakrishna, Suresh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198132/
https://www.ncbi.nlm.nih.gov/pubmed/34071237
http://dx.doi.org/10.3390/ijms22115766
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author Chandrasekaran, Arun Pandian
Woo, Sang Hyeon
Sarodaya, Neha
Rhie, Byung Ho
Tyagi, Apoorvi
Das, Soumyadip
Suresh, Bharathi
Ko, Na Re
Oh, Seung Jun
Kim, Kye-Seong
Ramakrishna, Suresh
author_facet Chandrasekaran, Arun Pandian
Woo, Sang Hyeon
Sarodaya, Neha
Rhie, Byung Ho
Tyagi, Apoorvi
Das, Soumyadip
Suresh, Bharathi
Ko, Na Re
Oh, Seung Jun
Kim, Kye-Seong
Ramakrishna, Suresh
author_sort Chandrasekaran, Arun Pandian
collection PubMed
description Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A.
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spelling pubmed-81981322021-06-14 Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis Chandrasekaran, Arun Pandian Woo, Sang Hyeon Sarodaya, Neha Rhie, Byung Ho Tyagi, Apoorvi Das, Soumyadip Suresh, Bharathi Ko, Na Re Oh, Seung Jun Kim, Kye-Seong Ramakrishna, Suresh Int J Mol Sci Article Cell division cycle 25A (Cdc25A) is a dual-specificity phosphatase that is overexpressed in several cancer cells and promotes tumorigenesis. In normal cells, Cdc25A expression is regulated tightly, but the changes in expression patterns in cancer cells that lead to tumorigenesis are unknown. In this study, we showed that ubiquitin-specific protease 29 (USP29) stabilized Cdc25A protein expression in cancer cell lines by protecting it from ubiquitin-mediated proteasomal degradation. The presence of USP29 effectively blocked polyubiquitination of Cdc25A and extended its half-life. CRISPR-Cas9-mediated knockdown of USP29 in HeLa cells resulted in cell cycle arrest at the G0/G1 phase. We also showed that USP29 knockdown hampered Cdc25A-mediated cell proliferation, migration, and invasion of cancer cells in vitro. Moreover, NSG nude mice transplanted with USP29-depleted cells significantly reduced the size of the tumors, whereas the reconstitution of Cdc25A in USP29-depleted cells significantly increased the tumor size. Altogether, our results implied that USP29 promoted cell cycle progression and oncogenic transformation by regulating protein turnover of Cdc25A. MDPI 2021-05-28 /pmc/articles/PMC8198132/ /pubmed/34071237 http://dx.doi.org/10.3390/ijms22115766 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chandrasekaran, Arun Pandian
Woo, Sang Hyeon
Sarodaya, Neha
Rhie, Byung Ho
Tyagi, Apoorvi
Das, Soumyadip
Suresh, Bharathi
Ko, Na Re
Oh, Seung Jun
Kim, Kye-Seong
Ramakrishna, Suresh
Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title_full Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title_fullStr Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title_full_unstemmed Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title_short Ubiquitin-Specific Protease 29 Regulates Cdc25A-Mediated Tumorigenesis
title_sort ubiquitin-specific protease 29 regulates cdc25a-mediated tumorigenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198132/
https://www.ncbi.nlm.nih.gov/pubmed/34071237
http://dx.doi.org/10.3390/ijms22115766
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