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Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP
The ubiquitin–proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific prote...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352364/ https://www.ncbi.nlm.nih.gov/pubmed/32545446 http://dx.doi.org/10.3390/cancers12061548 |
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author | Choi, Hae-Seul Pei, Chang-Zhu Park, Jun-Hyeok Kim, Soo-Yeon Song, Seung-Yeon Shin, Gyeong-Jin Baek, Kwang-Hyun |
author_facet | Choi, Hae-Seul Pei, Chang-Zhu Park, Jun-Hyeok Kim, Soo-Yeon Song, Seung-Yeon Shin, Gyeong-Jin Baek, Kwang-Hyun |
author_sort | Choi, Hae-Seul |
collection | PubMed |
description | The ubiquitin–proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific protease (HAUSP) is one such deubiquitinating enzyme and has been closely associated with tumor development. In a previous study, we isolated putative HAUSP binding substrates by two-dimensional electrophoresis (2-DE) and identified them by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The analysis showed that pyruvate kinase isoenzyme M2 (PKM2) was likely to be one of the substrates for HAUSP. Further study revealed that PKM2 binds to HAUSP, confirming the interaction between these proteins, and that PKM2 possesses the putative HAUSP binding motif, E or P/AXXS. Therefore, we generated mutant forms of PKM2 S57A, S97A, and S346A, and found that S57A had less binding affinity. In a previous study, we demonstrated that PKM2 is regulated by the UPS, and that HAUSP- as a DUB-acted on PKM2, thus siRNA for HAUSP increases PKM2 ubiquitination. Our present study newly highlights the direct interaction between HAUSP and PKM2. |
format | Online Article Text |
id | pubmed-7352364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73523642020-07-15 Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP Choi, Hae-Seul Pei, Chang-Zhu Park, Jun-Hyeok Kim, Soo-Yeon Song, Seung-Yeon Shin, Gyeong-Jin Baek, Kwang-Hyun Cancers (Basel) Article The ubiquitin–proteasome system (UPS) is responsible for proteasomal degradation, regulating the half-life of the protein. Deubiquitinating enzymes (DUBs) are components of the UPS and inhibit degradation by removing ubiquitins from protein substrates. Herpesvirus-associated ubiquitin-specific protease (HAUSP) is one such deubiquitinating enzyme and has been closely associated with tumor development. In a previous study, we isolated putative HAUSP binding substrates by two-dimensional electrophoresis (2-DE) and identified them by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF/MS) analysis. The analysis showed that pyruvate kinase isoenzyme M2 (PKM2) was likely to be one of the substrates for HAUSP. Further study revealed that PKM2 binds to HAUSP, confirming the interaction between these proteins, and that PKM2 possesses the putative HAUSP binding motif, E or P/AXXS. Therefore, we generated mutant forms of PKM2 S57A, S97A, and S346A, and found that S57A had less binding affinity. In a previous study, we demonstrated that PKM2 is regulated by the UPS, and that HAUSP- as a DUB-acted on PKM2, thus siRNA for HAUSP increases PKM2 ubiquitination. Our present study newly highlights the direct interaction between HAUSP and PKM2. MDPI 2020-06-12 /pmc/articles/PMC7352364/ /pubmed/32545446 http://dx.doi.org/10.3390/cancers12061548 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Choi, Hae-Seul Pei, Chang-Zhu Park, Jun-Hyeok Kim, Soo-Yeon Song, Seung-Yeon Shin, Gyeong-Jin Baek, Kwang-Hyun Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title | Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title_full | Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title_fullStr | Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title_full_unstemmed | Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title_short | Protein Stability of Pyruvate Kinase Isozyme M2 Is Mediated by HAUSP |
title_sort | protein stability of pyruvate kinase isozyme m2 is mediated by hausp |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352364/ https://www.ncbi.nlm.nih.gov/pubmed/32545446 http://dx.doi.org/10.3390/cancers12061548 |
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