The findings of Seung H. Choi, Ph.D., Jason B. Wright, Scott A. Gerber, Ph.D., and principal investigator Michael D. Cole, Ph.D., appear in the June issue of the peer-reviewed journal Genes & Development. The paper 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.
The team’s data suggest that inactivation of the Myc-degradation pathway can signal a preliminary step in cancer development.
“We want to know exactly what’s defective in tumor cells, and we keep coming back to the Myc protein,” explains Cole, a professor of pharmacology and toxicology and of genetics at Dartmouth Medical School (DMS). “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.”
Cole’s team found that in normal cells, the E3 ligase rids the cell of Myc after about 20 minutes (its half-life). In tumor cells, the function of this E3 ligase becomes inactive, extending Myc’s half-life to 40 and even 60 minutes.
“Understanding Myc is fundamental to understanding cancer cells,” says Dr. Cole, who has studied Myc for 28 years. “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.”
Choi, the lead author, is a research associate in the DMS Department of Pharmacology and Toxicology. Gerber is an assistant professor of genetics at DMS and with Cole is a member of Norris Cotton’s Cancer Mechanisms Research Program. Wright is a graduate student working in the Cole lab.
The Norris Cotton Cancer Center combines advanced cancer research at DMS with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center (DHMC), at Dartmouth-Hitchcock regional locations in Manchester and Keene, NH, and St. Johnsbury, Vt., and at 11 partner hospitals throughout New Hampshire and Vermont. It is one of 40 centers nationwide to have earned the National Cancer Institute’s “Comprehensive Cancer Center” designation. Learn more about research, programs, and clinical trials here.
Steve Bjerklie, Communications Coordinator, Norris Cotton Cancer Center, at Steven.P.Bjerklie@Dartmouth.edu or 603-653-9056.