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MTG-16 Regulation by Phosphorylation

Vanderbilt University
Michael Engel, MD, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
General Pediatric Cancer
Project Description: 

Cancer is a condition of uncontrolled cell growth and division. Cells must duplicate their genetic material, DNA, prior to cell division. This process requires a period of preparation by the cell. Having duplicated its DNA, the cell must reconfigure its resources to permit division into two daughter cells. These are extraordinarily complex processes that involve the contributions of many proteins working in a coordinated fashion. These processes are carefully regulated. Many of the regulatory proteins that control cell growth and division exert their effects by altering the function of other proteins with which they interact. Often the alteration occurs because the regulatory protein attaches a “chemical tag” to its target, causing the target to behave differently. One such chemical tag is a phosphate group, and proteins that are modified in this way are said to be phosphorylated. Normally, the altered behavior of a phosphorylated protein can be reversed by removal of the phosphate.

Much of what makes a cancer cell behave as it does reflects alterations in the expression of genes, and reversible phosphorylation of multiple proteins plays a major role in regulating gene expression. Understanding the fine details of how cells regulate gene expression is an essential first step toward controlling gene expression in cancer cells. To that end, we have defined a calss of proteins, called MTG proteins, that control gene expression and are frequently dysfunctional or non-functional in human cancers such as leukemia and breast cancer. When the normal function of these proteins is lost, the expression of many genes involved in cell growth and development is altered. We are attempting to understand how the MTG proteins control the expression of these genes and also to understand how MTG protein functions are regulated. We have shown that the function of MTG proteins might be changed by phosphorylation. How phosphorylation changes MTG protein function is not understood. Nor is the identity of the regulatory proteins that phosphorylate MTG known. Given the pivotal role for MTG proteins in cancer development, we believe a better understanding of how they function may lead to novel new treatments for diverse types of cancers in children and adults.