HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

ATM pathway is essential for ionizing radiation-induced autophagy.

AbstractBACKGROUND:
ATM plays an important role in response to DNA damage, while the roles of ATM in radiation-induced autophagy are still unclear in cervical cancer cells.
METHODS:
Human cervical cancer cells, Hela, were used, and cell models with ATM(-/-) and MAPK14(-/-) were established by gene engineering. Western blot was implemented to detect protein expression. MDC staining and GFP-LC3 relocalization were used to detect autophagy. CCK-8 was used to detect cell viability. Radiosensitivity was analyzed by colony formation assays. Co-immunoprecipitation was used to detect the interaction between different proteins, and apoptosis was detected by flow cytometry.
RESULTS:
After radiation autophagy was induced, illustrated by the increase of MAPLC3-II/MAPLC3-I ratio and decrease of p62, and phosphorylation of ATM simultaneously increased. ATM(-/-) cells displayed hypersensitivity but had no influence on IR-induced apoptosis. Then inhibitor of ATM, KU55933, ATM and MAPK14 silencing were used, and autophagy was induced by IR more than 200% in control, and only by 35.72%, 53.18% and 24.76% in KU55933-treated cells, ATM(-/-) and MAPK14(-/-) cells, respectively. KU55933 inhibited IR-induced autophagy by activating mTOR pathways. ATM silencing decreased the expression of MAPK14 and mTOR signals significantly. Beclin's bond to PI3KIII and their interaction increased after IR, while in ATM(-/-) and MAPK14(-/-) cells this interaction decreased after IR. Both ATM and MAPK14 interacted with Beclin, while ATM(-/-) and MAPK14(-/-) cells showed no interaction.
CONCLUSIONS:
ATM could promote IR-induced autophagy via the MAPK14 pathway, the mTOR pathway, and Beclin/PI3KIII complexes, which contributed to the effect of ATM on radiosensitivity.
AuthorsNan Liang, Lili Jia, Yang Liu, Bing Liang, Dejuan Kong, Mengmeng Yan, Shumei Ma, Xiaodong Liu
JournalCellular signalling (Cell Signal) Vol. 25 Issue 12 Pg. 2530-9 (Dec 2013) ISSN: 1873-3913 [Electronic] England
PMID23993957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013.
Chemical References
  • RNA, Small Interfering
  • Class III Phosphatidylinositol 3-Kinases
  • Ataxia Telangiectasia Mutated Proteins
  • TOR Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 14
Topics
  • Ataxia Telangiectasia Mutated Proteins (genetics, metabolism)
  • Autophagy (radiation effects)
  • Class III Phosphatidylinositol 3-Kinases (metabolism)
  • Female
  • HeLa Cells
  • Humans
  • Mitogen-Activated Protein Kinase 14 (genetics, metabolism)
  • RNA Interference
  • RNA, Small Interfering (genetics)
  • Radiation, Ionizing
  • Signal Transduction
  • TOR Serine-Threonine Kinases (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: