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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Shen, Changxian Houghton, Peter J. |
| Description | Author Affiliation: Shen C ( Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, Columbus, OH 43205, USA.); |
| Abstract | The ataxia telangiectasia mutated (ATM) checkpoint is the central surveillance system that maintains genome integrity. We found that in the context of childhood sarcoma, mammalian target of rapamycin (mTOR) signaling suppresses ATM by up-regulating miRNAs targeting ATM. Pharmacological inhibition or genetic down-regulation of the mTOR pathway resulted in increase of ATM mRNA and protein both in mouse sarcoma xenografts and cultured cells. mTOR Complex 1 (mTORC1) suppresses ATM via S6K1/2 signaling pathways. microRNA-18a and microRNA-421, both of which target ATM, are positively controlled by mTOR signaling. Our findings have identified a negative feedback loop for the signaling between ATM and mTOR pathways and suggest that oncogenic growth signals may promote tumorigenesis by dampening the ATM checkpoint. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 29 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Cycle Proteins Metabolism DNA-Binding Proteins Gene Expression Regulation, Neoplastic Physiology Protein-Serine-Threonine Kinases Sarcoma Signal Transduction TOR Serine-Threonine Kinases Tumor Suppressor Proteins Animals Ataxia Telangiectasia Mutated Proteins Cells, Cultured Feedback, Physiological Genetics Mice MicroRNAs Morpholines Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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