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oai:www.ideals.illinois.edu:2142/84792 2023-07-11 col_2142_5131 col_2142_14795 com_2142_5130 com_2142_14794 com_2142_14793 com_2142_8903

Chen, Jie Bachmann, Rebecca Anne 2015-09-25T22:27:55Z 2015-09-25T22:27:55Z 10000-01-01 2003 2003 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). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3086008.pdf: 5958312 bytes, checksum: f539155637f442ef75d1ee8ddf64296c (MD5) Previous issue date: 2003 Embargo set by: Seth Robbins for item 86073 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 123 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2003. http://hdl.handle.net/2142/84792 (MiAaPQ)AAI3086008 eng Health Sciences, Pharmacology Investigation of the Function and Regulatory Mechanisms of the Mammalian Target of Rapamycin text Biochemistry Biochemistry University of Illinois at Urbana-Champaign Dissertation Ph.D.