title: ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity.
abstract: OBJECTIVE
  Activation of the DNA damage responsive protein kinase ATM is a critical step for cellular survival in response to ionizing irradiation (IR). Direct targets of ATM regulating radiosensitivity remain to be fully investigated. We have recently reported that ATM phosphorylates the transcriptional repressor Snail on Serine 100. We aimed to further study the functional significance of ATM-mediated Snail phosphorylation in response to IR.
  
  
  METHODS
  We transfected vector-only, wild-type, the Serine 100 to alanine (S100A) or to glutamic acid (S100E) substitution of Snail into various cell lines. We assessed colony formation, γ-H2AX focus formation and the invasion index in the cells treated with or without IR.
  
  
  RESULTS
  We found that over-expression of the S100A mutant Snail in HeLa cells significantly increased radiosensitivity. Meanwhile the expression of S100E, a phospho-mimicking mutation, resulted in enhanced radio-resistance. Interestingly, S100E could rescue the radiosensitive phenotype in ATM-deficient cells. We also found that expression of S100E increased γ-H2AX focus formation and compromised inhibition of invasion in response to IR independent of cell survival.
  
  
  CONCLUSIONS
  ATM-mediated Snail Serine 100 phosphorylation in response to IR plays an important part in the regulation of radiosensitivity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, United States.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Boohaker
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Cui
authors.forename: Murray
authors.initials: M
authors.lastname: Stackhouse
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000502:physiology*; D006657:Histones / Q000032:analysis; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000532:radiotherapy*; D010766:Phosphorylation; D011836:Radiation Tolerance; D012694:Serine; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C468783:H2AX protein, human; D006657:Histones; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D012694:Serine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins
keywords: ATM; Radiosensitivity; Snail