Regulation of p53 translation following inhibition of dihydroorotate dehydrogenase (DHODH)

A novel class of DHODH inhibitors called tetrahydroindazoles was recently identified in the group of professor Sonia Lain through screening of a commercially available chemical library for activators of p53. The hit compound HZ00 is able to slow tumor cell growth in culture, an effect which was reversed upon supplementation with uridine, and had little effect on the growth of normal cells. The aim of this project is understanding the mechanisms that underlie increased translation of p53 mRNA after DHODH inhibition. For that purpose, we will study whether inhibition of DHODH by different DHODH inhibitors alters the expression of a set of selected proteins and small non-coding RNAs that regulate p53 translation. The selection will be based on mRNA and small RNA sequencing data. The expression of small RNAs, mRNAs and proteins of interest will be investigated using RT-qPCR, siRNA and WB analysis in different cell lines.

Faculty Supervisor:

Yuliya Lytvyn

Student:

Partner:

Karolinska Institute

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: