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Regulation of oncoproteins by deubiquitinating enzymes (DUBs) and their implications in the anti-cancer therapeutics

Title
Regulation of oncoproteins by deubiquitinating enzymes (DUBs) and their implications in the anti-cancer therapeutics
Author
Saba Haq
Alternative Author(s)
사바하크
Advisor(s)
Prof. Suresh Ramakrishna
Issue Date
2019-02
Publisher
한양대학교
Degree
Doctor
Abstract
Protein post-translational modifications (PTM) such as ubiquitination, deubiquitination, phosphorylation etc. are vital mechanisms in cellular regulation through affecting protein degradation, activity and signaling. LIN28A
an evolutionarily conserved RNA-binding protein has pivotal roles in cancers as aberrant expression of LIN28A is related to metastasis and poor prognosis. Till now, limited data is available regarding the post-translationalregulatory mechanisms involved in LIN28A protein stabilization and cancer progression. Herein, I report that LIN28A protein undergoes ubiquitination which is reversed by Ubiquitin-specific protease 28 (USP28). This research also demonstrates the consequential functional effects of USP28-mediated LIN28A protein stability on tumor progression. Overall, this research emphasizes the role of DUBs in contributing to effective cancer therapeutics. Reactive oxygen species (ROS) generation being pivotal for multiple cell signaling processes involved in proliferation and apoptosis is tightly regulated to check deleterious oxidizing effects causing carcinogenesis. NADPH oxidases catalyze cellular ROS generation via NOX-related proteins. Herein, I report the role of CYLD in regulating NOXO1 protein and subsequent ROS generation and cancer. This study suggests a novel therapeutic approach of targeting NOXO1 and ROS generation by CYLD enzyme.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/99333http://hanyang.dcollection.net/common/orgView/200000434694
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > LIFE SCIENCE(생명과학과) > Theses (Ph.D.)
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