Characterization of Signaling Events Induced by Low Dose Ionizing Radiation
EMSL Project ID
24390
Abstract
Exposure to low doses of radiation has the potential to adversely affect human health but the actual health risks and the underlying molecular mechanisms associated with these risks are still poorly understood. Therefore, new research is needed to understand how low dose radiation affects complex intracellular and extracellular regulatory pathways that keep carcinogenesis in check and maintain tissue homeostasis. We hypothesize that the initial response to low dose ionizing radiation is controlled by post-translational modifications on existing proteins that occur through activation of multiple signaling pathways regulated by both intracellular sensors of cell damage and extracellular signaling pathways that coordinate multicellular behavior in complex tissues. Specific combinations of post-translationally modified regulatory proteins may dictate individual cellular responses such as damage repair or cell death. Since many of the genes upregulated by low-dose exposure are components of signaling networks, altered post-translational modifications are likely to persist long after the initial exposures. Our proposal is designed to identify those proteins whose phosphorylation status is altered and provide mechanistic insight into the regulatory mechanisms governing the initial and sustained responses to low dose radiation. To accomplish this we will perform the following specific aims:1. Identify phosphoproteins and signaling pathways affected by low dose radiation in cells and tissues.
2. Develop phosphoproteomic profiles of specific phosphoproteins and protein complexes to identify the underlying molecular signatures that dictate the biological response to low dose radiation.
3. Define the molecular mechanisms that regulate adaptive responses to low dose radiation in cells and tissues.
Project Details
Project type
Scientific Partner
Start Date
2007-05-03
End Date
2008-05-04
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
Hengel S, JT Aldrich, KM Waters, L Pasa-Tolic, and DL Stenoien. 2014. "Quantitative Proteomic Profiling of Low Dose Ionizing Radiation Effects in a Human Skin Model." Proteomes 2(3):382-398. doi:10.3390/proteomes2030382
Zhao R, SJ Ding, Y Shen, DG Camp, II, EA Livesay, HR Udseth, and RD Smith. 2009. "Automated metal-free multiple-column nanoLC for improved phosphopeptide analysis sensitivity and throughput." Journal of Chromatography B 877(8-9):663-670.