After discovering a key protein in the process of cell division, a team of researchers at Norris Cotton Cancer Center is one step closer to understanding the long-standing mysteries of uncontrollable tumor cell multiplication. The researchers’ findings, published this month in the journal Genes & Development, present new information about the way that Myc protein, which initiates cell division in both healthy and cancerous cells, is regulated by a previously unknown protein called E3 ligase.
Seung Choi, the paper’s primary author, began isolating a group of proteins tightly bound to Myc protein almost five years ago at Norris Cotton. Working with DMS professor Scott Gerber, who coauthored the paper, Choi sequenced the proteins and discovered that E3 ligase regulates cell division by breaking down Myc protein.
Normal cells have a half-life of roughly 20 minutes, but when E3 ligase is deactivated the cell’s half-life doubles to 40 minutes, according to DMS professor Michael Cole, one of the paper’s coauthors.
Their research supports past findings that high levels of Myc protein, which helps regulate cell division and is necessary for cell survival, can lead to the growth of tumor cells.
The early discovery of the Myc protein’s role in cancer development makes it one of the more commonly studied genes in cancer research, Cole said. The researchers’ discovery of E3 ligase protein is an important stride toward understanding the relationship between Myc protein and tumor development, according to Cole.
“This is good solid science that unravels a step in this pathway,” he said.
Various theories have been proposed to explain the slow turnover of tumor cells but Cole, who has worked with Myc protein for 28 years, said he has “never believed them.”
“There’s been a long-standing controversy about why Myc protein turns over so quickly,” Cole said. “People have noted that tumor cells have a prolonged half-life but have never understood why.”
It is not currently understood why tumor cells fail to breakdown the Myc protein, a problem that Cole expressed interest in exploring for future research projects.
Gerber, who works in a laboratory that identifies and characterizes cell proteins and protein functions, came to Cole’s lab at Norris Cotton to help identify other proteins involved in Myc protein functions, including the E3 ligase. Gerber was able to use new technologies to identify proteins that allowed the team to conduct research that would have been impossible ten years ago and very difficult five years ago, he said.
Choi said he will further investigate the interaction between Myc and other cancer genes in future research in the hopes of providing insight into how to develop effective cancer medications.
The paper was also coauthored by Jason Wright.