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An interaction between mTOR and Myc in cell size control
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González, Luis Steven Servín (2021) An interaction between mTOR and Myc in cell size control. PhD thesis, University of Warwick.
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Official URL: http://webcat.warwick.ac.uk/record=b3765582
Abstract
Regulation of cell size is controlled by multiple biochemical pathways, such as the mammalian target of rapamycin (mTOR) signalling pathway and the transcription factor Myc. The loss of tightly regulated control of cell size is known to be associated with multiple diseases such as cancer. Understanding how key molecular components in such pathways is necessary to elucidate the mechanisms behind cell size control. Since pathways consist of large networks of interacting molecules, changes in the expression of such molecules may have a large impact on the signalling cascade output, therefore investigating the impact of how the growth-regulating signalling cascade is affected by hampering expression of effectors involved in the pathway is of great interest. This thesis shows that chemical and siRNA downregulation of central pathway effectors of the mTOR pathway reduces cell size and volume, which also change the cell cycle distribution. Furthermore, RNAseq analysis from a dataset similar to our experiments showed that differentially expressed genes from cells exposed to rapamycin seem to be involved in ribosomal biogenesis and metabolism.
We observed that over-expression of Myc lead to notable increases in cell size and volume which were linked to higher levels of protein and rRNA content. RNAseq analysis of this cells showed that differentially expressed genes seemed to be involved in different cellular mechanisms related to cell size. Remarkably, Myc over expressing cells that were exposed to the mTOR inhibitor Rapamycin had a size like non-treated cells but with higher content of protein and rRNA. Sequencing analysis from these cells revealed many down-regulated genes involved in cell metabolism, translation, and other cellular process. A combination of Rapamycin and the rRNA synthesis inhibitor, Actinomycin D reduced the size and rRNA content of the Myc overexpressing cells, suggesting that ribosome biogenesis could be the mechanism behind the size control. To identify an alternative effector involved in cell size and ribosome biogenesis, we show that incubation of cells with a p38 MAPK inhibitor further reduces cell size and rRNA content, suggesting a possible interaction between the PI3K/AKT/mTOR pathway, with the p38 MAPK pathway and Myc.
| Item Type: | Thesis (PhD) | ||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| Library of Congress Subject Headings (LCSH): | Cells -- Growth, Cells -- Growth -- Regulation, Transcription factors, Rapamycin, Cellular control mechanisms | ||||
| Official Date: | January 2021 | ||||
| Dates: |
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| Institution: | University of Warwick | ||||
| Theses Department: | School of Life Sciences | ||||
| Thesis Type: | PhD | ||||
| Publication Status: | Unpublished | ||||
| Supervisor(s)/Advisor: | Hebenstreit, Daniel, 1977- | ||||
| Sponsors: | Consejo nacional de ciencia y tecnología (México | ||||
| Format of File: | |||||
| Extent: | vi, 154 leaves : illustrations | ||||
| Language: | eng |
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