{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T07:04:16Z","timestamp":1791529456864,"version":"4.3.4"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,3,2]]},"abstract":"<jats:p>\n                    Ataxia-telangiectasia mutated (ATM) is a cellular damage sensor that coordinates the cell cycle with damage-response checkpoints and DNA repair to preserve genomic integrity. However, ATM also has been implicated in metabolic regulation, and ATM deficiency is associated with elevated reactive oxygen species (ROS). ROS has a central role in many physiological and pathophysiological processes including inflammation and chronic diseases such as atherosclerosis and cancer, underscoring the importance of cellular pathways involved in redox homeostasis. We have identified a cytoplasmic function for ATM that participates in the cellular damage response to ROS. We show that in response to elevated ROS, ATM activates the TSC2 tumor suppressor via the LKB1\/AMPK metabolic pathway in the cytoplasm to repress mTORC1 and induce autophagy. Importantly, elevated ROS and dysregulation of mTORC1 in ATM-deficient cells is inhibited by rapamycin, which also rescues lymphomagenesis in\n                    <jats:italic>Atm<\/jats:italic>\n                    -deficient mice. Our results identify a cytoplasmic pathway for ROS-induced ATM activation of TSC2 to regulate mTORC1 signaling and autophagy, identifying an integration node for the cellular damage response with key pathways involved in metabolism, protein synthesis, and cell survival.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0913860107","type":"journal-article","created":{"date-parts":[[2010,2,16]],"date-time":"2010-02-16T23:49:50Z","timestamp":1266364190000},"page":"4153-4158","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":658,"title":["ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS"],"prefix":"10.1073","volume":"107","author":[{"given":"Angela","family":"Alexander","sequence":"first","affiliation":[{"name":"Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957;"},{"name":"Graduate School of Biomedical Sciences, University of Texas Health Science Center, Houston TX 77030;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Li","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Nanez","sequence":"additional","affiliation":[{"name":"Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Neurobiology Program, Department of Neurology, Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsteen H.","family":"MacLean","sequence":"additional","affiliation":[{"name":"Department of Oncology, St. Jude Children\u2019s Research Hospital, Memphis, TN 38105;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Inoki","sequence":"additional","affiliation":[{"name":"Life Sciences Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Liang","family":"Guan","sequence":"additional","affiliation":[{"name":"Moores Cancer Center, University of California, San Diego, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville, TX 78957;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria D.","family":"Person","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Texas, Austin TX 78712; 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