Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/53682
Title: Characterization of the Cellular response to Hypoxia
Authors: TAN CHIA YEE
Keywords: mTORC1, Hypoxia, Reoxygenation, REDD1, CDC6, Degradation
Issue Date: 17-Jan-2014
Source: TAN CHIA YEE (2014-01-17). Characterization of the Cellular response to Hypoxia. ScholarBank@NUS Repository.
Abstract: Hypoxia exerts a strong inhibitory effect on mTORC1 activity. However, the mechanistic basis is currently not well understood. In my study I found that oxygen concentrations regulate mTORC1 activity in a highly dynamic manner. This rapid response of mTORC1 to changes in oxygen concentrations is independent of HIF or its transcriptional targets, REDD1 and BNIP3. The effect of hypoxia on mTORC1 is mediated through a posttranslational mechanism that likely involves a hemecontaining protein. In further studies I characterized the posttranslational regulation of REDD1 and CDC6. REDD1 is a negative regulator of mTORC1 that is transcriptionally upregulated in hypoxia. My study shows that mTORC1 increases REDD1 protein stability and reveals a novel mTORC1-REDD1 feedback loop. Finally, I found that the cell cycle-regulatory protein CDC6 is not regulated by hypoxia but is rapidly degraded upon cellular exposure to DNA-damaging agents in a manner dependent on the ubiquitin-like protein Nedd8.
URI: http://scholarbank.nus.edu.sg/handle/10635/53682
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
TanCY.pdf7.65 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

175
checked on Dec 11, 2017

Download(s)

198
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.