Publication

mTOR under stress

Heberle, A. M., 2019, [Groningen]: University of Groningen. 292 p.

Research output: ThesisThesis fully internal (DIV)Academic

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  • Title and contents

    Final publisher's version, 288 KB, PDF document

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  • Summary

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  • Samenvatting

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  • Chapter 1

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  • Chapter 2

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  • Chapter 3

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  • Chapter 4

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  • Chapter 5 Publisher's version

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  • Chapter 5

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  • Chapter 6

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  • Chapter 7

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  • Acknowledgements

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  • Curriculum vitae and publications

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  • Complete thesis

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  • Propositions

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The mechanistic/ mammalian target of rapamycin complex 1 (mTORC1) is a metabolic master regulator which integrates amino acid, growth factor, and energy signals to control cellular metabolism. mTORC1 kinase enhances virtually all anabolic processes and inhibits catabolism to promote cell growth. Under stress, mTORC1 also promotes cell survival. Therefore, mTORC1 activity is needed both under favorable and unfavorable conditions to enable growth and survival, respectively. However, mTORC1 hyperactivity leads to cell death due to uncoupling of metabolism and growth from regulatory inputs. Hence, mTORC1 activity has to be finely tuned to (i) promote anabolic processes and cell growth when nutrients are sufficient, and (ii) balance anabolic and catabolic processes and allow cell survival under stress. While the molecular mechanisms mediating anabolic inputs to mTORC1 have been reported in much detail, mechanistic studies on stress-signaling to mTORC1 and mTORC1-mediated adaptation of cellular metabolism are comparably scarce. This thesis centers on the mechanisms which balance mTORC1 activity and function under stress. We identified novel mechanisms that balance anabolic and catabolic processes to sustain survival under stress. Our findings suggest a novel Achilles heel, which can be targeted in cancer.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Supervisors/Advisors
Award date20-Feb-2019
Place of Publication[Groningen]
Publisher
Print ISBNs9789463235013
Electronic ISBNs9789463235020
Publication statusPublished - 2019

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