To investigate how RACK1 facilitates the activity, substrate specificity and cellular location of PP2A in mammary epithelial cells

Key Information

Cancer type: 
Breast
Research Institution: 
UL
Grant Amount: 
€120,000
Start date: 
October 1, 2011
End date: 
September 30, 2014

Scientific Project Abstract

Imagine hundreds of actors cast to act out a battle scene in a blockbuster movie. The cameras are on, the lighting is perfect but nobody can find the script and nobody can find the Director. This results in chaos and panic! The scene does not get filmed because nobody knows what to do! Genes and proteins are found inside living cells. They are like actors in a big battle scene which takes place inside the cell. Most of the time, just like in the films, the good guys win. The genes and proteins win because they are produced and directed to carry out a specific job, they have a specific role to play. But, like the movie scene, when systems break down and the director is missing or the script gets lost, the genes and proteins forget where they are, they forget what they were supposed to do which results in chaos. RACK1 is a protein which interacts with other proteins and directs them where to go inside the cell, in this way it is like the Director in our movie.

Dr Kiely's research has shown that RACK1 binds to another protein called PP2A. PP2A is a tumour suppressor, which means that its normal role inside the cell is like that of a security guard, keeping other proteins 'in check' and making sure that all proteins behave properly. Everything is fine when RACK1 and PP2A are working together to 'keep the peace'. When normal systems break down inside a cell, we believe that there is a change in the relationship between RACK1 and PP2A. They don't get along anymore. PP2A does not 'keep the peace' like it used to. It becomes deregulated and this leads to the development of breast cancer. I want to find out what causes the change and breakdown in the relationship between RACK1 and PP2A and what happens to the other proteins in the cell when the security guard PP2A is away. I believe that if we work hard to understand this breakdown, we will be able to design ways of restoring the order and peace in the cell again, allowing all the proteins to act like normal.

For the non-scientist

One-line description: 
Unravelling the regulatory mechanism of an important cancer suppressor molecule in breast cancer
What this project involves: 

This project aims to understand a key cellular mechanism which, when deregulated, leads to the development of breast cancer. The study aims to understand the relationship between two molecules, RACK1 and a tumour suppressor molecule called PP2A. In normal cells, RACK1 and PP2A work together to maintain PP2A's tumour suppressor role, however, when there is a change in this relationship, cancer develops. This project aims to why this change in the relationship between RACK1 and PP2A occurs and find ways of restoring it.