Year: 2022
Type: dissertation
Abstract: While molecules that promote the growth of animal cells have been identified, it remains unclear how such signals are orchestrated to determine and maintain a characteristic target size for the different cell types. More recent studies have established that cell size is determined by size checkpoints – mechanisms that restrict the cell cycle progression of cells that are smaller than their target size. However, what determines such a target size remains unclear. Through a chemical screen and subsequent validation studies, I have identified CDK4 activity to set the critical size referenced to by homeostatic mechanisms in proliferating animal cells (Chapter 2). In other words, CDK4 activity shifts the size threshold at which checkpoint mechanisms consider a cell to be ‘too small’. While these findings shed light on the molecular processes involved with target size determination, the cell size checkpoint remains limited in rectifying cells that are too large. To that end, I followed up on previous reports highlighting mechanisms of growth rate regulation (i.e., how fast cells accumulate mass) that function in parallel with size checkpoints to maintain cell size homeostasis. It has been shown that large cells slow down rates of growth; however, mechanistic studies on such a compensatory response are lacking. I have demonstrated that large cells inhibit growth not by slowing down protein production but rather by upregulating rates of protein degradation (Chapter 3). Together, these findings contribute insights into the mechanisms that control cell size in animal cells.
Source: TSpace (University of Toronto)
Author: Tan, Ceryl Elvira
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7132960918