title: Annexin A2 modulates radiation-sensitive transcriptional programming and cell fate.
abstract: We previously established annexin A2 as a radioresponsive protein associated with anchorage independent growth in murine epidermal cells. In this study, we demonstrate annexin A2 nuclear translocation in human skin organotypic culture and murine epidermal cells after exposure to X radiation (10-200 cGy), supporting a conserved nuclear function for annexin A2. Whole genome expression profiling in the presence and absence of annexin A2 [shRNA] identified fundamentally altered transcriptional programming that changes the radioresponsive transcriptome. Bioinformatics predicted that silencing AnxA2 may enhance cell death responses to stress in association with reduced activation of pro-survival signals such as nuclear factor kappa B. This prediction was validated by demonstrating a significant increase in sensitivity toward tumor necrosis factor alpha-induced cell death in annexin A2 silenced cells, relative to vector controls, associated with reduced nuclear translocation of RelA (p65) following tumor necrosis factor alpha treatment. These observations implicate an annexin A2 niche in cell fate regulation such that AnxA2 protects cells from radiation-induced apoptosis to maintain cellular homeostasis at low-dose radiation.
authors.affiliation: Computational Biology and Bioinformatics, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Waters
authors.forename: David L
authors.initials: DL
authors.lastname: Stenoien
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Sowa
authors.forename: Claere
authors.initials: C
authors.lastname: von Neubeck
authors.forename: William B
authors.initials: WB
authors.lastname: Chrisler
authors.forename: Ruimin
authors.initials: R
authors.lastname: Tan
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Sontag
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Weber
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D000818:Animals; D017306:Annexin A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects; D020868:Gene Silencing; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D012867:Skin / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects*; D059467:Transcriptome / Q000187:drug effects / Q000528:radiation effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014965:X-Rays / Q000009:adverse effects
chemical_list: D017306:Annexin A2; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha