cpilling

The first human protein discovered to be a potent tumor driver was the tyrosine kinase Src. After over 40 years of research on Src we know that over expression rather then genetic mutation of Src results in its powerful tumor driver phenotype; however, we still do not understand how a cell maintains the proper amount of Src protein thereby preventing tumor formation.  The goal of my work in the Cooper lab is to identify and map the mechanism the ubiquitin proteasome system uses to control Src protein levels.  More specifically I am interested in understanding how the E3-ubiquitin ligase Cullin5 regulates Src protein levels.

We know that active Src protein levels go up when Cullin5 is deleted from epithelial cells and this results in transformation of these cells.  My goals in the Cooper lab are 1) Identify the substrate adaptor Cullin5 uses to recognize Src 2) Identify the Degron directing Src to Cullin5 3) Determine if interactions between Cullin5 substrate adaptor proteins and Src are direct or indirect.  This will give us a better understanding the molecular switch that can be manipulated turning normal cell growth to the uncontrolled growth state know as cancer.