Deciphering the roles of scaffold proteins (IQGAP1 and IQGAP2) and xenosensor (CAR) in liver biology

The liver is essential for bile synthesis, coordinating intermediary metabolism, energy storage, and detoxification. Its many functions routinely expose it to a wide range of insults. The liver responds and adapts to these stressors using molecular regulators such as scaffold proteins and nuclear receptors. This dissertation examines the role of scaffold proteins (IQGAP1 and IQGAP2) and a nuclear receptor (CAR) in modulating the liver’s response to physiological and pathological stressors. Chapter 2 reviews the role of nuclear receptors in combating oxidative stress within the liver. Chapter 3 investigates the role of CAR during pesticide exposure within the liver. For instance, the absence of CAR led to imidacloprid pesticide accumulation in the liver and altered detoxification gene expression. Chapter 4 examines the role of scaffold protein IQGAP2 in maintaining liver metabolic homeostasis. Analysis of Iqgap2-/- mice and IQGAP2-depleted cells revealed IQGAP2’s mechanistic role in regulating AKT, GSK3, and FOXO3 phosphorylation and subsequent hepatic glycogen accumulation during fed-state response. Chapter 5 examines the role of IQGAP1 during cholestatic injury. The absence of IQGAP1 led to increased bile acid accumulation and liver injury. Overall, these results elucidate new roles of scaffold proteins, IQGAP1 and IQGAP2, and nuclear receptor CAR in contributing to liver function in health and disease states.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Molecular & Integrative Physi

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2023

Author dc:creator

• Sen, Anushna

Contributors dc:contributor

• Anakk, Sayeepriyadarshini
• Raetzman, Lori T
• Tsai, Nien-Pei
• Brieher, William M

• Liver
• Scaffold Proteins
• Iqgap1
• Iqgap2
• Car
• Nuclear Receptor
• Environmental Toxicant
• Pesticide
• Metabolism
• Insulin Signaling
• Cholestasis
• Liver Injury

Statement dc:rights

• Copyright 2023 Anushna Sen

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/121324

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F121324