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PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress

Ribonucleotide reductase small subunit B (RRM2B) is a stress response protein that protects normal human fibroblasts from oxidative stress. However, the underlying mechanism that governs this function is not entirely understood. To identify factors that interact with RRM2B and mediate anti-oxidation...

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Autores principales: Kuo, Mei-Ling, Lee, Mabel Bin-Er, Tang, Michelle, den Besten, Willem, Hu, Shuya, Sweredoski, Michael J., Hess, Sonja, Chou, Chih-Ming, Changou, Chun A., Su, Mingming, Jia, Wei, Su, Leila, Yen, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702135/
https://www.ncbi.nlm.nih.gov/pubmed/26733354
http://dx.doi.org/10.1038/srep18846
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author Kuo, Mei-Ling
Lee, Mabel Bin-Er
Tang, Michelle
den Besten, Willem
Hu, Shuya
Sweredoski, Michael J.
Hess, Sonja
Chou, Chih-Ming
Changou, Chun A.
Su, Mingming
Jia, Wei
Su, Leila
Yen, Yun
author_facet Kuo, Mei-Ling
Lee, Mabel Bin-Er
Tang, Michelle
den Besten, Willem
Hu, Shuya
Sweredoski, Michael J.
Hess, Sonja
Chou, Chih-Ming
Changou, Chun A.
Su, Mingming
Jia, Wei
Su, Leila
Yen, Yun
author_sort Kuo, Mei-Ling
collection PubMed
description Ribonucleotide reductase small subunit B (RRM2B) is a stress response protein that protects normal human fibroblasts from oxidative stress. However, the underlying mechanism that governs this function is not entirely understood. To identify factors that interact with RRM2B and mediate anti-oxidation function, large-scale purification of human Flag-tagged RRM2B complexes was performed. Pyrroline-5-carboxylate reductase 1 and 2 (PYCR1, PYCR2) were identified by mass spectrometry analysis as components of RRM2B complexes. Silencing of both PYCR1 and PYCR2 by expressing short hairpin RNAs induced defects in cell proliferation, partial fragmentation of the mitochondrial network, and hypersensitivity to oxidative stress in hTERT-immortalized human foreskin fibroblasts (HFF-hTERT). Moderate overexpression of RRM2B, comparable to stress-induced level, protected cells from oxidative stress. Silencing of both PYCR1 and PYCR2 completely abolished anti-oxidation activity of RRM2B, demonstrating a functional collaboration of these metabolic enzymes in response to oxidative stress.
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spelling pubmed-47021352016-01-14 PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress Kuo, Mei-Ling Lee, Mabel Bin-Er Tang, Michelle den Besten, Willem Hu, Shuya Sweredoski, Michael J. Hess, Sonja Chou, Chih-Ming Changou, Chun A. Su, Mingming Jia, Wei Su, Leila Yen, Yun Sci Rep Article Ribonucleotide reductase small subunit B (RRM2B) is a stress response protein that protects normal human fibroblasts from oxidative stress. However, the underlying mechanism that governs this function is not entirely understood. To identify factors that interact with RRM2B and mediate anti-oxidation function, large-scale purification of human Flag-tagged RRM2B complexes was performed. Pyrroline-5-carboxylate reductase 1 and 2 (PYCR1, PYCR2) were identified by mass spectrometry analysis as components of RRM2B complexes. Silencing of both PYCR1 and PYCR2 by expressing short hairpin RNAs induced defects in cell proliferation, partial fragmentation of the mitochondrial network, and hypersensitivity to oxidative stress in hTERT-immortalized human foreskin fibroblasts (HFF-hTERT). Moderate overexpression of RRM2B, comparable to stress-induced level, protected cells from oxidative stress. Silencing of both PYCR1 and PYCR2 completely abolished anti-oxidation activity of RRM2B, demonstrating a functional collaboration of these metabolic enzymes in response to oxidative stress. Nature Publishing Group 2016-01-06 /pmc/articles/PMC4702135/ /pubmed/26733354 http://dx.doi.org/10.1038/srep18846 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kuo, Mei-Ling
Lee, Mabel Bin-Er
Tang, Michelle
den Besten, Willem
Hu, Shuya
Sweredoski, Michael J.
Hess, Sonja
Chou, Chih-Ming
Changou, Chun A.
Su, Mingming
Jia, Wei
Su, Leila
Yen, Yun
PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title_full PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title_fullStr PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title_full_unstemmed PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title_short PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
title_sort pycr1 and pycr2 interact and collaborate with rrm2b to protect cells from overt oxidative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702135/
https://www.ncbi.nlm.nih.gov/pubmed/26733354
http://dx.doi.org/10.1038/srep18846
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