OBJECTIVES: The role of Ataxia-telangiectasia mutated (ATM) in response to DNA 
damage has previously been studied, but its underlying mechanisms specific to 
ionizing radiation (IR) have remained to be elucidated. In this study, function 
of ATM on radiation-induced cell death in lung cancer H1299 cells was analysed.
MATERIALS AND METHODS: Human lung cancer cells, H1299, were used, and cell 
models with ATM(-/-) and MAPK14(-/-) were established by genetic engineering. 
Radiosensitivity was analysed using colony formation assays. Western blotting 
and co-immunoprecipitation were implemented to detect protein expression and 
interaction. MDC staining and GFP-LC3 relocalization were used to detect 
autophagy.
RESULTS: Autophagy as well as phosphorylation of ATM was activated by ionizing 
radiation. Both the inhibitor of ATM, KU55933 and ATM silencing reduced 
phosphorylation of ATM and MAPKAPK2 expression. Both ATM(-/-) and MAPK14(-/-) 
cells displayed hypersensitivity. IR increased autophagy level by more than 129% 
in DMSO-treated cells, while only by 47% and 27% in KU55933-treated and ATM(-/-) 
cells respectively. MAPK14 knock-down alone gave rise to the basal autophagy 
level, but decreased notably after IR. KU55933 and ATM knock-down inhibited 
IR-induced autophagy by activating mTOR pathways. Both Beclin1-PI3KIII and 
Beclin1-MAPKAPK2 interactions as were remarkably affected by silencing either 
ATM or MAPK14.
CONCLUSIONS: ATM promoted IR-induced autophagy via the MAPK14 pathway, mTOR 
pathway and Beclin1/PI3KIII complexes. MAPK14 contributed to radiosensitization 
of H1299 cells.