Deubiquitinating Enzymes as Novel Anticancer Targets
Deubiquitinating Enzymes as Novel Anticancer Targets
Investigator
Li Ma, PhD
Associate Professor
Department of Experimental Radiation Oncology, Division of Radiation Oncology
The University of Texas MD Anderson Cancer Center
Houston, Texas
Summary
A growing number of oncoproteins (proteins that promote tumor growth) and pro-metastatic proteins (proteins that promote the spread of tumor cells from the original tumor site/organ) have been extensively characterized. However, many of these cancer-promoting proteins have not themselves provided opportunities for development of new drugs. There is a need, therefore, for alternative therapeutic strategies directed toward cancer-promoting proteins. Much attention has been paid to a small protein called ubiquitin that is found in almost all tissues and serves as a tag that helps signal to cells how to regulate other proteins. Enzymes called deubiquitinating enzymes, or DUBs, remove ubiquitin from proteins thereby modifying function. The hypothesis in this research proposal is that DUBs substantially regulate key cancer proteins and pathways, thereby promoting tumor cell growth and metastases. Although DUBs have been considered as good candidates for drug development, no DUB inhibitors have entered the clinic. In humans there are 79 DUBs, providing a wealth of possible drug targets. This proposal aims to identify and target DUBs so as to inactivate some key oncoproteins or pro-metastatic proteins either by destabilizing these proteins or by changing their activity. Dr. Ma’s laboratory has already identified the first DUB that suppresses tumors by regulating the key anticancer protein, PTEN. In this study, Dr. Ma will screen a library of DUBs for those that regulate key oncoproteins and pro-metastatic proteins. In parallel, she will determine which DUBs promote tumorigenesis, metastasis, or therapy resistance. The identified cancer-promoting DUBs will be tested for the ability to serve as anticancer targets, paving the way for developing DUB inhibitors as new cancer drugs.
Updated: May 2016