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

Mei Ling Kuo, Mabel Bin Er Lee, Michelle Tang, Willem Den Besten, Shuya Hu, Michael J. Sweredoski, Sonja Hess, Chih Ming Chou, Chun A. Changou, Mingming Su, Wei Jia, Leila Su, Yun Yen

研究成果: 雜誌貢獻文章

24 引文 (Scopus)

摘要

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.
原文英語
文章編號18846
期刊Scientific Reports
6
DOIs
出版狀態已發佈 - 一月 6 2016

指紋

Oxidative Stress
Pyrroline Carboxylate Reductases
Fibroblasts
Ribonucleotide Reductases
Foreskin
Heat-Shock Proteins
Small Interfering RNA
Mass Spectrometry
Hypersensitivity
Cell Proliferation
Enzymes

ASJC Scopus subject areas

  • General

引用此文

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.

於: Scientific Reports, 卷 6, 18846, 06.01.2016.

研究成果: 雜誌貢獻文章

Kuo, ML, Lee, MBE, Tang, M, Den Besten, W, Hu, S, Sweredoski, MJ, Hess, S, Chou, CM, Changou, CA, Su, M, Jia, W, Su, L & Yen, Y 2016, 'PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress', Scientific Reports, 卷 6, 18846. https://doi.org/10.1038/srep18846
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. 於: Scientific Reports. 2016 ; 卷 6.
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abstract = "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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