The "anti-cancer" protein of naked diggers
Researchers at the University of Rochester, working under the guidance of Professor Vera Gorbunova and associate Professor Andrey Seluanov, have identified a protein that can explain the resistance of naked diggers to cancer.
Naked diggers (Heterocephalus glaber) are small rodents living in burrows and having no hair covering, the uniqueness of which lies not only in their 30–year lifespan, but also in their resistance to the development of cancer.
The authors identified a protein associated with a cluster (locus) of INK4 genes in the body of a naked digger, an analog of which is found in the genomes of humans and mice. This genetic locus encodes instructions for the synthesis of a number of proteins with antitumor effect. According to Professor Gorbunova, in the case of a naked digger, this locus encodes 4 proteins, whereas its mouse and human versions only have 3 proteins each.
According to the results of earlier studies, the INK4 locus encodes the same proteins – p15 INK4b, p16 INK4a and ARF – both in mice and in humans. The functions of all three proteins are to stop the division of a cell exposed to stress factors or having mutated genes. When studying the p16 INK4a protein in the body of a naked digger, a fourth, previously unknown protein of this group was unexpectedly discovered, which is the result of the fusion of p15 INK4b and p16 INK4a protein molecules.
Later it was found that this hybrid protein, called pALT INK4a/b, stops the division of damaged cells no worse, if not better, than the original proteins forming it.
To determine the significance of the hybrid protein pALT INK4a/b, the researchers analyzed the expression of proteins under various conditions of cell growth. It turned out that the level of hybrid protein increases in a crowded population of cells under the condition of the presence of hyaluronic acid with a high molecular weight (HMW-HA). Earlier studies by the authors showed that the content of a large amount of this compound in the tissues of naked diggers protects them from cancer by activating the INK4 genetic locus.
On the other hand, pALT INK4a/b expression was not recorded in the absence of HMW-HA, but was restored under the influence of a number of stress stimuli, such as oncogenes, potentially capable of causing cancer development.
Based on observations, the researchers concluded that the hybrid protein pALT INK4a/b increases the ability of naked diggers to stop cell division when there is a risk of malignancy compared to animals with only 3 genes encoded by the INK4 locus.
Attempts to identify the hybrid protein pALT INK4a/b in the tissues and cells of mice and humans have not been successful. However, the authors argue that this does not exclude the possibility of its occurrence in the organisms of mice and humans under special conditions, but only indicates a low probability of this.
The article by Xiao Tian et al. INK4locus of the tumor-resistant rodent, the naked mole rat, expresses a functional p15/p16 hybrid isoform published in the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of Rochester:
An extra protein gives naked mole rats more power to stop cancer.
10.02.2015