title: Functional proteomics analysis to study ATM dependent signaling in response to ionizing radiation.
abstract: Ataxia telangiectasia (AT) is a human genetic disease characterized by radiation sensitivity, impaired neuronal development and predisposition to cancer. Using a genetically defined model cell system consisting of cells expressing a kinase dead or a kinase proficient ATM gene product, we previously reported systemic alterations in major metabolic pathways that translate at the gene expression, protein and small molecule metabolite levels. Here, we report ionizing radiation induced stress response signaling arising from perturbations in the ATM gene, by employing a functional proteomics approach. Functional pathway analysis shows robust translational and post-translational responses under ATM proficient conditions, which include enrichment of proteins in the Ephrin receptor and axonal guidance signaling pathways. These molecular networks offer a hypothesis generating function for further investigations of cellular stress responses.
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.|Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors: Amrita K
authors: AK
authors: Cheema
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Rency S
authors: RS
authors: Varghese
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Olga
authors: O
authors: Timofeeva
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Lihua
authors: L
authors: Zhang
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Alexander
authors: A
authors: Kirilyuk
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Fereshteh
authors: F
authors: Zandkarimi
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Prabhjit
authors: P
authors: Kaur
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.
authors: Habtom W
authors: HW
authors: Ressom
authors: Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors: Mira
authors: M
authors: Jung
authors: Department of Oncology, Georgetown University Medical Center, Washington, DC.|Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC.
authors: Anatoly
authors: A
authors: Dritschilo
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction / Q000528:radiation effects*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases
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