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PYCR1 and PYCR2 Interact and Collaborate with RRM2B to Protect Cells from Overt Oxidative Stress.
- Source :
-
Scientific reports [Sci Rep] 2016 Jan 06; Vol. 6, pp. 18846. Date of Electronic Publication: 2016 Jan 06. - Publication Year :
- 2016
-
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.
- Subjects :
- Animals
Antioxidants metabolism
Cell Cycle Checkpoints
Cell Cycle Proteins genetics
Cell Line
Gene Knockdown Techniques
Gene Silencing
Humans
Isoenzymes
Mass Spectrometry methods
Mitochondria genetics
Mitochondria metabolism
Multiprotein Complexes metabolism
Protein Binding
Protein Interaction Mapping
Protein Transport
Pyrroline Carboxylate Reductases genetics
Recombinant Fusion Proteins
Ribonucleotide Reductases genetics
Signal Transduction
Telomerase genetics
Telomerase metabolism
Tumor Suppressor Protein p53 metabolism
Zebrafish
delta-1-Pyrroline-5-Carboxylate Reductase
Cell Cycle Proteins metabolism
Oxidative Stress
Pyrroline Carboxylate Reductases metabolism
Ribonucleotide Reductases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26733354
- Full Text :
- https://doi.org/10.1038/srep18846