PUBLICATION
PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress
- Authors
- Kuo, M.L., Lee, M.B., Tang, M., den Besten, W., Hu, S., Sweredoski, M.J., Hess, S., Chou, C.M., Changou, C.A., Su, M., Jia, W., Su, L., Yen, Y.
- ID
- ZDB-PUB-170214-54
- Date
- 2016
- Source
- Scientific Reports 6: 18846 (Journal)
- Registered Authors
- Keywords
- Cell signalling, Protein–protein interaction networks
- MeSH Terms
-
- Animals
- Antioxidants/metabolism
- Cell Cycle Checkpoints
- Cell Cycle Proteins/genetics
- Cell Cycle Proteins/metabolism*
- Cell Line
- Gene Knockdown Techniques
- Gene Silencing
- Humans
- Isoenzymes
- Mass Spectrometry/methods
- Mitochondria/genetics
- Mitochondria/metabolism
- Multiprotein Complexes/metabolism
- Oxidative Stress*
- Protein Binding
- Protein Interaction Mapping
- Protein Transport
- Pyrroline Carboxylate Reductases/genetics
- Pyrroline Carboxylate Reductases/metabolism*
- Recombinant Fusion Proteins
- Ribonucleotide Reductases/genetics
- Ribonucleotide Reductases/metabolism*
- Signal Transduction
- Telomerase/genetics
- Telomerase/metabolism
- Tumor Suppressor Protein p53/metabolism
- Zebrafish
- PubMed
- 26733354 Full text @ Sci. Rep.
Citation
Kuo, M.L., Lee, M.B., Tang, M., den Besten, W., Hu, S., Sweredoski, M.J., Hess, S., Chou, C.M., Changou, C.A., 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. 6:18846.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping