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Published on: March 20, 2021
ATM-mediated Snail Serine 100 phosphorylation regulates cellular radiosensitivity
Rebecca J Boohaker1, Xiaoli Cui, Murray Stackhouse
1Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, United States.
Summary
ATM-mediated Snail phosphorylation at Serine 100 regulates cellular response to ionizing radiation (IR). This finding is crucial for understanding radiosensitivity and developing targeted cancer therapies.
Area of Science:
- Cellular Biology
- Molecular Oncology
- Radiation Biology
Background:
- ATM (Ataxia-telangiectasia mutated) is a key kinase activated by DNA damage from ionizing radiation (IR).
- ATM's direct targets influencing radiosensitivity require further investigation.
- ATM phosphorylates the transcriptional repressor Snail on Serine 100.
Purpose of the Study:
- To investigate the functional role of ATM-mediated Snail phosphorylation at Serine 100 in response to IR.
- To elucidate the impact of Snail phosphorylation on cellular radiosensitivity.
Main Methods:
- Transfection of various Snail constructs (wild-type, S100A, S100E) into cell lines.
- Assessment of colony formation, γ-H2AX focus formation, and invasion index after IR exposure.
- Evaluation in ATM-deficient cells to confirm ATM-dependent effects.
Main Results:
- Overexpression of Snail S100A mutant increased radiosensitivity.
- Snail S100E (phospho-mimicking) enhanced radio-resistance and rescued radiosensitivity in ATM-deficient cells.
- S100E expression increased γ-H2AX foci and impaired invasion inhibition post-IR, independent of cell survival.
Conclusions:
- ATM-mediated Snail phosphorylation at Serine 100 is a significant regulator of radiosensitivity.
- Targeting Snail phosphorylation could offer novel strategies for modulating cancer cell response to radiation therapy.
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