A newly found protein may be the naked mole rat’s secret weapon in warding off cancer.
The hairless, subterranean rodents don’t appear to get cancer despite having a 30-year lifespan.
The new protein is associated with a cluster of genes, called a locus, that is also found in humans and mice. It’s the job of that locus to encode—or carry the genetic instructions for synthesizing —several cancer-fighting proteins. The locus found in naked mole rats encodes a total of four cancer-fighting proteins. The human and mouse version encodes only three.
The findings are published in the Proceedings of the National Academy of Sciences.
Stop the cancer
Researchers know that the genes in question—referred to as INK4 gene locus—synthesize the same three cancer-suppressing proteins in both species: p15INK4b, p16INK4a, and ARF, all of which stop cells from dividing when the cells are stressed or mutated.
Researchers wanted to clone the p16 protein of the naked mole rat for a separate experiment and noticed something unexpected: The presence of a fourth protein, which was the result of p15INK4b and p16INK4a being fused together.
This fourth protein was as good or even better than p15INK4b and p16INK4a at stopping cells from dividing, says Vera Gorbunova, professor of biology at University of Rochester.
“We named this novel product pALTINK4a/b and we believe it may contribute to the longevity of the naked mole rat, including its ability to prevent tumors from developing.”
Previous research by Gorbunova and colleague Andrei Seluanov identified HMW-HA as the chemical that activates the anti-cancer response of the INK4 locus.
“INK4 is the most commonly mutated gene locus in the human cancer,” Seluanov says. “When that gene is deleted or silenced, it often results in the formation of tumors.” There is also growing evidence to support the protein’s role in atherosclerosis and other aging-related diseases.
“Considering how mutations in the INK4 gene are linked to human cancers,” Gorbunova says, “the better we understand that gene and control its mutations, the better our chances of controlling some cancers.”
In order to determine the significance of pALTINK4a/b, researchers examined the expression of the proteins under different cell growth conditions and found the presence of the hybrid protein does increase when cells become crowded, as long as HMW-HA is present.
On the other hand, when HMW-HA was removed, pALTINK4a/b was not expressed, but it was also induced by a variety of stresses such as oncogenes, which have the potential to cause cancer. The researchers conclude that the protein does respond to high-cell density and to HMW-HA, which initiates the anti-cancer response of the INK4 gene.
The presence of the fourth protein makes naked mole rats more likely to stop growth when there is a risk of malignancy, compared to other mammals that have only three proteins, the researchers say.
To see whether the extra protein is also found in mice and humans, researchers tried to screen mouse and human cells and tissues for the protein hybrid, but were unsuccessful.
“While our work doesn’t eliminate the possibility that the protein exists under some conditions in mice and humans, the results suggest that it’s highly unlikely,” Gorbunova says.
Other researchers from University of Rochester and from Harvard University and Albert Einstein College of Medicine are coauthors of the study.
Source: University of Rochester