Novel Ser/Thr Protein Phosphatase 5 (PP5) Regulated Targets during DNA Damage Identified by Proteomics Analysis
The DNA damage response is a global phosphorylation signaling cascade process involved in sensing the damaged DNA condition and coordinating responses to cope with and repair the perturbed cellular state. We utilized a label-free liquid chromatography-mass spectrometry approach to evaluate changes in protein phosphorylation associated with PP5 activity during the DNA damage response. Biological replicate analyses of bleomycin-treated HeLa cells expressing either WT-PP5 or mutant inactive PP5 lead to the identification of six potential target proteins of PP5 action. Four of these putative targets are known to be involved in DNA damage responses. Using phospho-site specific antibodies, we confirmed that phosphorylation of one target, ribosomal protein S6, was selectively decreased in cells overexpressing catalytically inactive PP5. Our findings also suggest that PP5 may play a role in controlling translation and in regulating substrates for proline-directed kinases, such as MAP kinases and cyclin-dependent protein kinases that are involved in response to DNA damage.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Environmental Molecular Sciences Lab. (EMSL)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 974919
- Report Number(s):
- PNNL-SA-69020; 24698; KP1602020; TRN: US201007%%878
- Journal Information:
- Journal of Proteome Research, 9(2):945-953, Vol. 9, Issue 2
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
60 APPLIED LIFE SCIENCES
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
ANTIBODIES
DNA
DNA DAMAGES
HELA CELLS
MUTANTS
PHOSPHATASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
REPAIR
SPECTROSCOPY
SUBSTRATES
TARGETS
Environmental Molecular Sciences Laboratory