The Resurrected Anti - Oncogene
"Genetic zombie" protects elephants from cancer
Sergey Vasiliev, Naked Science
Elephants live about as long as humans, and contain hundreds of times more cells – and each of them can turn into a tumor during their lifetime. However, if the mortality rate from cancer in humans reaches 17 percent, then elephants do not exceed five. It turns out that, in terms of cell, their resistance to cancer is orders of magnitude greater than ours. This feature intrigues scientists, forcing them to look for mechanisms that allow the elephant's body to prevent the development of cancer so effectively.
A few years ago, the team of Vincent Lynch, a professor at the University of Chicago, showed that this ability is partially related to the gene of the p53 protein, a transcription factor involved in the regulation of the cell cycle and the suppression of malignant tumors. Most cancer cells are mutated by p53, however, as Lynch and colleagues found out, elephant DNA contains as many as 20 copies of p53, each of which is able to protect the body in case of cell degeneration.
In a new article published in the journal Cell Reports (Vazquez et al., A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in Response to DNA Damage), Vincent Lynch and co-authors described another gene that plays an important role in "antitumor protection" in elephants. More precisely, we are talking about a pseudogene – a site that has lost its functionality as a result of an inherited mutation. Elephants have eight such pseudogenes that once encoded protein factors that inhibit leukemia (Leukemia Inhibitory Factor, LIF). And one of them, the LIF6 gene, randomly acquired a new "switch".
As scientists have shown, elephant LIF6 is triggered by the active protein p53 (which, in turn, reacts to the appearance of damaged DNA). The LIF6 factor quickly migrates to the mitochondria and disrupts the permeability of their membranes, blocking the processes of cellular respiration and causing the damaged cell to die without the possibility of giving rise to a whole tumor. The authors compare this gene to a zombie that is "raised from the dead" to kill – individual cells, but for the benefit of the whole organism.
The pseudogene became active in the ancestors of elephants about 25-30 million years ago, about the same time when the increase in the size of their still tiny body began; perhaps it was this mutation that became the key and provided modern elephants with a long quiet life with minimal risk of cancer.
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