CHARACTERIZATION OF PDX1 AND ITS INTERACTIONS WITH SPOP

Restricted (Penn State Only)
Author:
Brittingham, Jacob Charles
Graduate Program:
Molecular, Cellular and Integrative Biosciences
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
August 15, 2018
Committee Members:
  • Scott A Showalter, Thesis Advisor
  • Melissa Rolls, Committee Member
  • Lorraine C Santy, Committee Member
Keywords:
  • PDX1
  • SPOP
Abstract:
PDX1 is a transcription factor that regulates a variety of glucose responsive pathways within pancreatic tissue. However, its primary function is to control the expression of insulin within β-cells. PDX1 mutations predispose people to both type-2 diabetes as well as specific forms of pancreatic cancers. While the relationship between PDX1 and insulin is well understood, there is significant controversy on what the exact co-factors are and how they regulate PDX1. In this work, we explore a novel binding site for PDX1 and its degradation partner SPOP. Through a combination of biological assays, we attempt to characterize this new binding region and its effect on a variety of cell lines. Furthermore, we explore a few other co-factors in the hope to characterize the effects of known clinical mutants. We found these experiments allow us to identify the cause of specific mutants in hopes of developing new therapeutic targets.