OTULIN's Novel Regulatory Mechanisms in Genotoxic and Inflammatory NF-kB Signaling

<p>Triple negative breast cancer (TNBC) is aggressive but cannot be treated with hormone therapy or molecular therapy due to the lack of a target. Chemotherapy is a systemic treatment that works by attacking rapidly growing cells, which is initially more effective for TNBC patients than those individuals with the hormone receptor-positive breast cancer. However, patients with TNBC tend to develop resistance to chemo drugs, called chemoresistance. After years of effort, the signaling pathways involved in TNBC chemoresistance are gradually revealed, including the nuclear factor-kappa B (NF-kB) pathway. Transcription factor NF-kB is widely involved in cancer development and progression, and its overactivation renders chemoresistance to TNBC and induces aberrant inflammation. Therefore, targeting NF-kB becomes a feasible strategy to overcome chemoresistance. Ubiquitination is an essential post-translational modification during which ubiquitin chains are assembled on a substrate protein, leading to various cellular processes, such as endocytosis, membrane trafficking, DNA repair, signal transduction, and protein degradation. The outcome of one ubiquitinated protein is dependent on its ubiquitin linkage and the context. Our previous study has shown that the linear ubiquitin chains assembled by the linear ubiquitin chain assembly complex (LUBAC) solidly facilitate NF-kB signaling transduction upon genotoxic stress. OTU deubiquitinase with linear linkage specificity (OTULIN) is known to cleave linear ubiquitin chains exclusively. The purpose of this dissertation is to investigate whether OTULIN can counteract LUBAC-mediated NF-</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2022

Author dc:creator

• Li, Mingqi

Contributors dc:contributor

• Francesca-Fang Liao, Ph.D.

• chemoresistance; inflammation; LUBAC; NF-kB; OTULIN; TNF-alpha
• Diseases
• Medicine and Health Sciences
• Neoplasms
• Therapeutics

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/610

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1610