Journal article
Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation
PloS one, Vol.5(11), pp.e14152-e14152
11/30/2010
Handle:
https://hdl.handle.net/2376/116782
PMCID: PMC2994767
PMID: 21152398
Abstract
High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation.
We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation.
Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.
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Details
- Title
- Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation
- Creators
- Feng Yang - Pacific Northwest National Laboratory, Richland, Washington, United States of AmericaKatrina M WatersJohn H MillerMarina A GritsenkoRui ZhaoXiuxia DuEric A LivesaySamuel O PurvineMatthew E MonroeYingchun WangDavid G Camp, 2ndRichard D SmithDavid L Stenoien
- Publication Details
- PloS one, Vol.5(11), pp.e14152-e14152
- Academic Unit
- Engineering and Applied Sciences (TRIC), School of
- Publisher
- United States
- Grant note
- RR18522 / NCRR NIH HHS P41 RR018522 / NCRR NIH HHS
- Identifiers
- 99900547764301842
- Language
- English
- Resource Type
- Journal article