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Title:Investigation of the Function and Regulatory Mechanisms of the Mammalian Target of Rapamycin
Author(s):Bachmann, Rebecca Anne
Doctoral Committee Chair(s):Chen, Jie
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Health Sciences, Pharmacology
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.
Issue Date:2003
Description:123 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2003.
Other Identifier(s):(MiAaPQ)AAI3086008
Date Available in IDEALS:2015-09-25
Date Deposited:2003

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