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New Study Helps Explain Protein Function in Tumor Cell Growth

New research from the Cancer Center helps explain why the Myc protein, found in the nucleus of cells and crucial to the function of cell division, sometimes reaches elevated levels that cause it to be an agent in the growth of cancerous tumors.

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Michael Cole, PhD

Published in the peer-review journal Genes & Development, the research by scientists Seung H. Choi, PhD; Jason B. Wright; Scott A. Gerber, PhD; and Michael D. Cole, PhD; identifies a novel protein complex, E3 ligase, that in normal cells regulates the degradation of Myc protein. In tumor cells, however, this degradation is significantly dampened.

Dr. Choi and Jason Wright work in the laboratory of Dr. Cole, who began studying the Myc protein 28 years ago. Dr. Gerber is a Professor of Genetics whose specialty is the large-scale analysis of proteins called proteomics. Together, Dr. Gerber and Dr. Cole use proteomics to understand how cancer functions and how certain proteins are involved in tumor growth.

Proteins are the workhorses of the human body. Antibodies are proteins; so are some hormones. There are hundreds of thousands, even millions, of unique protein forms—many more than the number of genes in human DNA. Identifying and understanding all the possible protein combinations that impact the human body and human health is a daunting task, especially when considering the mechanisms that push cells to become cancerous. But progress is being made—proteomics has been called the next big step in cancer research.

The Cole team's data suggest that inactivation of the Myc-degradation pathway can be a preliminary step in cancer development. In tumor cells, Myc becomes a kind of super growth-promoter. "We want to know exactly what's defective in tumor cells, and we keep coming back to the Myc protein," explains Cole. "The more Myc you have, the more cell growth you have. For some reason, in cancer cells the regulation of Myc is disrupted and tumor cells grow like the accelerator is on the floor all the time."

He adds, "Understanding Myc is fundamental to understanding cancer cells. In this paper we are able to show cause and effect for Myc degradation. What we still need to understand is why, in tumor cells, the degradation machinery for Myc is turned off."

October 26, 2010