Protein-Protein Interactions Involving Liver Receptor Homolog 1 (LRH-1) in Pancreatic Adenocarcinoma Open Access

Abstract

Liver Receptor Homolog-1 (LRH-1), also known as NR5A2 (Nuclear Receptor Subfamily 5, Group A, Member 2), is a nuclear receptor that plays a critical role in the regulation of various physiological processes. Initially identified as a liver-enriched pioneer factor regulating cholesterol transport and bile acid production, LRH-1 is recognized for its role as a transcription factor expressed in multiple tissues, including the liver, pancreas, intestine, and reproductive organs. In Pancreatic Adenocarcinoma, LRH-1 transcription is highly upregulated and is correlated with increased pancreatic tumor growth. While LRH-1 co-localization on chromatin with oncogenic proteins has been observed, direct interaction between LRH-1 and such proteins has yet to be shown. Potential interactions between LRH-1 and several proteins known to play roles in cancer growth and metastasis in cancer were measured using a BRET assay, which measures interaction strength by emitting a fluorescent signal upon binding interaction between a Nano-luciferase tagged LRH-1 and a venus tagged-protein.

Table of Contents

Introduction

Pancreatic Adenocarcinoma 

LRH-1 Hippo Pathway

Wnt Pathway

Proteins of Interest (POIs)

Research Aims and Hypothesis

Methods

Cell Culture

Vector Construct Design

Gateway Cloning

DNA purification

BRET Assay

Results

BRET Optimization

BRET Trial

Discussion

Contributions to Science

Study Limitations

Future Direction

References

About this Honors Thesis

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School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Physiology Biology, Cell
Keyword	PDAC LRH-1
Committee Chair / Thesis Advisor	Eric Ortlund, Emory University
Committee Members	Iain Shepherd, Emory University Greg Lesinski, Emory University

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