ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity

Abstract Purpose 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 tran...

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Bibliographic Details
Published in:Radiotherapy and oncology 2013-09, Vol.108 (3), p.403-408
Main Authors: Boohaker, Rebecca J, Cui, Xiaoli, Stackhouse, Murray, Xu, Bo
Format: Article
Language:English
Subjects:
Ataxia Telangiectasia Mutated Proteins - physiology
ATM
Hematology, Oncology and Palliative Medicine
Histones - analysis
Humans
Neoplasm Invasiveness
Neoplasms - radiotherapy
Phosphorylation
Radiation Tolerance
Radiosensitivity
Serine
Snail
Snail Family Transcription Factors
Transcription Factors - metabolism
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Summary:Abstract Purpose 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. Material and 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. Conclusion ATM-mediated Snail Serine 100 phosphorylation in response to IR plays an important part in the regulation of radiosensitivity.
ISSN:0167-8140
1879-0887
DOI:10.1016/j.radonc.2013.06.017