Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/121915
Title: CELLULAR MECHANISMS INVOLVED IN AGEING AND AGE-RELATED DISEASES
Authors: HONG SHIN YEE
Keywords: Ageing, TXNIP, Metabolism, ER stress, Cancer
Issue Date: 21-Aug-2015
Citation: HONG SHIN YEE (2015-08-21). CELLULAR MECHANISMS INVOLVED IN AGEING AND AGE-RELATED DISEASES. ScholarBank@NUS Repository.
Abstract: In this project, I addressed a number of important questions related to ageing and the major age-associated disease cancer. I investigated the potential role of mitochondrial protein acylation in ageing associated mitochondrial dysfunction. I found that mitochondrial protein acylation, specifically succinylation, increases with age in C. elegans and D. melanogaster (but not in rodents). This suggests that protein acylation may contribute to ageing associated mitochondrial dysfunction in these organisms. In relation to cancer, I studied the regulation of thioredoxin interacting protein (TXNIP). TXNIP is known to inhibit cellular glucose metabolism. I showed that growth factor signalling inhibits TXNIP expression, which may explain at least in part the observation that TXNIP is frequently downregulated in cancer. My data also suggest that downregulation of TXNIP in cancers with constitutive growth factor signaling may contribute to the Warburg effect by increasing cellular glucose uptake. Furthermore, 2-deoxyglucose, which has been used in clinical cancer trials, upregulated TXNIP expression via O-GlcNAcylation. This suggests a potential strategy to therapeutically induce TXNIP expression in cancer cells. Finally, I studied the mechanism of proteasome inhibitor treatment resistance in multiple myeloma. I found evidence for a role of mutation in the endoplasmic stress response factor XBP1 in mediating proteasome inhibitor resistance. In conclusion, my results suggest that deregulation of mitochondrial protein acylation, cellular glucose metabolism and the cellular ER stress response contribute to ageing and ageing-associated diseases.
URI: http://scholarbank.nus.edu.sg/handle/10635/121915
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
HongSH__Redacted.pdf6.39 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

139
checked on May 29, 2020

Google ScholarTM

Check


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