{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/84792"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/84792","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Investigation of the Function and Regulatory Mechanisms of the Mammalian Target of Rapamycin","abstract":"Unexpectedly, mTOR has been found to shuttle between the nucleus and the cytoplasm, and this shuttling is required for its cytoplasmic signaling. I have further investigated the regulation and function of mTOR cytoplasmic-nuclear shuttling. A systematic screen of mTOR revealed a rev-like NES sequence within mTOR at amino acids 1281--1289, which displayed robust nuclear export activity in a reporter system. Mutation of the conserved leucines within this export site resulted in a loss of downstream signaling in vivo, despite retention of mTOR catalytic activity. Interestingly, the mTOR 1281--1289L/A mutant showed cytoplasmic staining similar to wild type mTOR, and did not accumulate in the nucleus upon LMB treatment. This suggests that the 1281--1289L/A mutations in mTOR disrupt nucleocytoplasmic shuttling activity. The nucleocytoplasmic shuttling of mTOR is likely a mechanism to lessen the probability of aberrant signaling, a necessary control for a protein that has an essential role in cell growth and proliferation.","abstract_html":"Unexpectedly, mTOR has been found to shuttle between the nucleus and the cytoplasm, and this shuttling is required for its cytoplasmic signaling. I have further investigated the regulation and function of mTOR cytoplasmic-nuclear shuttling. A systematic screen of mTOR revealed a rev-like NES sequence within mTOR at amino acids 1281--1289, which displayed robust nuclear export activity in a reporter system. Mutation of the conserved leucines within this export site resulted in a loss of downstream signaling in vivo, despite retention of mTOR catalytic activity. Interestingly, the mTOR 1281--1289L/A mutant showed cytoplasmic staining similar to wild type mTOR, and did not accumulate in the nucleus upon LMB treatment. This suggests that the 1281--1289L/A mutations in mTOR disrupt nucleocytoplasmic shuttling activity. The nucleocytoplasmic shuttling of mTOR is likely a mechanism to lessen the probability of aberrant signaling, a necessary control for a protein that has an essential role in cell growth and proliferation.","abstract_has_math":false,"creators":["Bachmann, Rebecca Anne"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Chen, Jie"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-25T22:27:55Z","date_published":"2015-09-25T22:27:55Z","updated_at":"2026-07-22T22:26:23Z","subjects":["Health Sciences, Pharmacology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3086008"],"render_values":[{"text":"(MiAaPQ)AAI3086008","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/84792","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chen, Jie"]},{"key":"dc:creator","label":"Author","values":["Bachmann, Rebecca Anne"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-25T22:27:55Z","10000-01-01","2003"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health Sciences, Pharmacology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/84792","(MiAaPQ)AAI3086008"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Unexpectedly, mTOR has been found to shuttle between the nucleus and the cytoplasm, and this shuttling is required for its cytoplasmic signaling. I have further investigated the regulation and function of mTOR cytoplasmic-nuclear shuttling. A systematic screen of mTOR revealed a rev-like NES sequence within mTOR at amino acids 1281--1289, which displayed robust nuclear export activity in a reporter system. Mutation of the conserved leucines within this export site resulted in a loss of downstream signaling in vivo, despite retention of mTOR catalytic activity. Interestingly, the mTOR 1281--1289L/A mutant showed cytoplasmic staining similar to wild type mTOR, and did not accumulate in the nucleus upon LMB treatment. This suggests that the 1281--1289L/A mutations in mTOR disrupt nucleocytoplasmic shuttling activity. The nucleocytoplasmic shuttling of mTOR is likely a mechanism to lessen the probability of aberrant signaling, a necessary control for a protein that has an essential role in cell growth and proliferation.","Made available in DSpace on 2015-09-25T22:27:55Z (GMT). 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I have further investigated the regulation and function of mTOR cytoplasmic-nuclear shuttling. A systematic screen of mTOR revealed a rev-like NES sequence within mTOR at amino acids 1281--1289, which displayed robust nuclear export activity in a reporter system. Mutation of the conserved leucines within this export site resulted in a loss of downstream signaling in vivo, despite retention of mTOR catalytic activity. Interestingly, the mTOR 1281--1289L/A mutant showed cytoplasmic staining similar to wild type mTOR, and did not accumulate in the nucleus upon LMB treatment. This suggests that the 1281--1289L/A mutations in mTOR disrupt nucleocytoplasmic shuttling activity. The nucleocytoplasmic shuttling of mTOR is likely a mechanism to lessen the probability of aberrant signaling, a necessary control for a protein that has an essential role in cell growth and proliferation.","Made available in DSpace on 2015-09-25T22:27:55Z (GMT). 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