Crosstalk of the mTOR network with stress granules and the TGF-beta pathway

Mirja Tamara Prentzell

Crosstalk of the mTOR network with stress granules and the TGF-beta pathway

Mirja Tamara Prentzell

Research output: Thesis › Thesis fully internal (DIV)

1825 Downloads (Pure)

Abstract

All organisms and cells need nutrients in order to grow and survive. The protein kinase mTOR (mechanistic or mammalian target of rapamycin) is a signaling hub that senses nutrients and promotes cell growth in all eukaryotes. mTOR is embedded in a complex signaling network whose dysregulation leads to severe malfunction and a variety of diseases, including cancer and neurological disorders.

This thesis centers on mechanisms of mTOR crosstalk with two other cellular signaling networks governing cellular growth and survival. The first aim of this thesis was to characterize the interplay between mTOR and stress granules, cytoplasmic non-membranous RNA-protein assemblies. Stress granules are dynamic entities, which form upon stresses that arrest protein synthesis. The second aim was to unravel mTOR’s crosstalk with the transforming growth factor beta (TGF-beta) pathway. TGF-beta has key roles in organismal development and cancer by controlling processes such as cell proliferation, survival and migration.

Our findings suggest that mTOR crosstalk with stress granules and the TGF-beta pathway influences the effects of drugs targeting the mTOR network, warranting further investigation in the context of targeted cancer therapies.

Translated title of the contribution	Wisselwerkingen tussen het mTOR netwerk met stress granules en de TGF-beta signaleringsroute
Original language	English
Qualification	Doctor of Philosophy
Awarding Institution	University of Groningen
Supervisors/Advisors	Thedieck, Kathrin, Supervisor Baumeister, Ralf, Supervisor, External person Opitz, C, Supervisor, External person Baumeister, Ralf, Assessment committee, External person Opitz, C, Assessment committee, External person Foijer, Floris, Assessment committee Sers, Christine, Assessment committee, External person
Award date	7-May-2018
Place of Publication	[Groningen]
Publisher	University of Groningen
Print ISBNs	978-94-034-0632-9
Electronic ISBNs	978-94-034-0631-2
Publication status	Published - 2018

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Title and contentsFinal publisher's version, 738 KB
SummariesFinal publisher's version, 607 KB
Chapter 1Final publisher's version, 5.34 MB
Chapter 2Final publisher's version, 4.06 MB
Chapter 3Final publisher's version, 27.3 MB
Chapter 4Final publisher's version, 5.66 MB
Chapter 5Final publisher's version, 2.79 MB
Chapter 6Final publisher's version, 12.9 MB
Chapter 7Final publisher's version, 17.5 MB
Chapter 8Final publisher's version, 659 KB
Curriculum VitaeFinal publisher's version, 569 KB
List of publicationsFinal publisher's version, 579 KB
AcknowledgementsFinal publisher's version, 572 KB
Complete thesisFinal publisher's version, 72.3 MB
PropositionsFinal publisher's version, 218 KB

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title = "Crosstalk of the mTOR network with stress granules and the TGF-beta pathway",

abstract = "All organisms and cells need nutrients in order to grow and survive. The protein kinase mTOR (mechanistic or mammalian target of rapamycin) is a signaling hub that senses nutrients and promotes cell growth in all eukaryotes. mTOR is embedded in a complex signaling network whose dysregulation leads to severe malfunction and a variety of diseases, including cancer and neurological disorders. This thesis centers on mechanisms of mTOR crosstalk with two other cellular signaling networks governing cellular growth and survival. The first aim of this thesis was to characterize the interplay between mTOR and stress granules, cytoplasmic non-membranous RNA-protein assemblies. Stress granules are dynamic entities, which form upon stresses that arrest protein synthesis. The second aim was to unravel mTOR{\textquoteright}s crosstalk with the transforming growth factor beta (TGF-beta) pathway. TGF-beta has key roles in organismal development and cancer by controlling processes such as cell proliferation, survival and migration. Our findings suggest that mTOR crosstalk with stress granules and the TGF-beta pathway influences the effects of drugs targeting the mTOR network, warranting further investigation in the context of targeted cancer therapies.",

author = "Prentzell, {Mirja Tamara}",

year = "2018",

language = "English",

isbn = "978-94-034-0632-9",

publisher = "University of Groningen",

school = "University of Groningen",

}

TY - BOOK

T1 - Crosstalk of the mTOR network with stress granules and the TGF-beta pathway

AU - Prentzell, Mirja Tamara

PY - 2018

Y1 - 2018

N2 - All organisms and cells need nutrients in order to grow and survive. The protein kinase mTOR (mechanistic or mammalian target of rapamycin) is a signaling hub that senses nutrients and promotes cell growth in all eukaryotes. mTOR is embedded in a complex signaling network whose dysregulation leads to severe malfunction and a variety of diseases, including cancer and neurological disorders. This thesis centers on mechanisms of mTOR crosstalk with two other cellular signaling networks governing cellular growth and survival. The first aim of this thesis was to characterize the interplay between mTOR and stress granules, cytoplasmic non-membranous RNA-protein assemblies. Stress granules are dynamic entities, which form upon stresses that arrest protein synthesis. The second aim was to unravel mTOR’s crosstalk with the transforming growth factor beta (TGF-beta) pathway. TGF-beta has key roles in organismal development and cancer by controlling processes such as cell proliferation, survival and migration. Our findings suggest that mTOR crosstalk with stress granules and the TGF-beta pathway influences the effects of drugs targeting the mTOR network, warranting further investigation in the context of targeted cancer therapies.

AB - All organisms and cells need nutrients in order to grow and survive. The protein kinase mTOR (mechanistic or mammalian target of rapamycin) is a signaling hub that senses nutrients and promotes cell growth in all eukaryotes. mTOR is embedded in a complex signaling network whose dysregulation leads to severe malfunction and a variety of diseases, including cancer and neurological disorders. This thesis centers on mechanisms of mTOR crosstalk with two other cellular signaling networks governing cellular growth and survival. The first aim of this thesis was to characterize the interplay between mTOR and stress granules, cytoplasmic non-membranous RNA-protein assemblies. Stress granules are dynamic entities, which form upon stresses that arrest protein synthesis. The second aim was to unravel mTOR’s crosstalk with the transforming growth factor beta (TGF-beta) pathway. TGF-beta has key roles in organismal development and cancer by controlling processes such as cell proliferation, survival and migration. Our findings suggest that mTOR crosstalk with stress granules and the TGF-beta pathway influences the effects of drugs targeting the mTOR network, warranting further investigation in the context of targeted cancer therapies.

M3 - Thesis fully internal (DIV)

SN - 978-94-034-0632-9

PB - University of Groningen

CY - [Groningen]

ER -

Crosstalk of the mTOR network with stress granules and the TGF-beta pathway

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