A special gene in elephants could hold the key to eradicating cancers

Despite their enormous size and long life, elephants are surprisingly resistant to cancer, which is why their DNA may contain the answer to warding off cancers.

A team of scientists from seven different research institutes used bioinformatics modeling to examine the molecular connections of the protein p53, known to defend the body against cancers, according to a press release from the University of Oxford.

According to a study published in Molecular biology and evolution. With further exploration, this could have many implications for cancer treatments in humans.

Elephant genes and cancer

Each time a cell divides, new cells replace old ones with new copies of DNA. While these new cells should be exact replicas of older cells, mutations can occur which are quickly repaired by the cell most of the time.

However, genetic and environmental factors impact the amount of mutations and the quality of repairs. Aging, stress, unhealthy living conditions, and toxic substances can all accelerate the rate of mutation. Cancer develops when cells divide out of control and invade nearby tissues, and tumors caused by the accumulation of genetic mutations grow at risk with age.

However, when it comes to elephants, known for their massive bodies and human lifespans, they seem to defy this trend.

Tumors caused by the accumulation of genetic mutations increase in risk with age, but elephants seem to defy this trend. In fact, less than five percent of elephants are expected to die of cancer, compared to up to 25 percent in humans. According to the scientists, this resistance is attributed to the 20 copies of the p53 gene in elephants, as opposed to the only one seen in other mammals.

P53: “The guardian of the genome”

In case you didn’t know, p53 is important for controlling DNA repair pathways and suppressing uncontrolled cell growth. When DNA is damaged, the protein activates and helps orchestrate a response that stops DNA replication and corrects any incorrect copies of the cell.

p53 repair activity is not required in cells duplicated with undamaged DNA and is inhibited by another protein, the oncogene MDM2 E3 ubiquitin ligase. The elephant may have 40 alleles of its twenty p53 genes, but each is physically slightly different. This allows the elephant a significantly broader spectrum of molecular anti-cancer interactions than a human, with only two versions of a single gene.

In the new study, the researchers uncovered crucial discrepancies in the initial interaction between multiple elephant p53 isoforms and MDM2, through biochemical studies and computer simulations.

The researchers found that due to alterations in coding sequences and molecular structure, a number of p53s avoided the interaction with MDM2 that would normally lead to deactivation. This is crucial because the results are the first to indicate that, unlike humans, MDM2 does not degrade or inactivate the many p53 isoforms seen in elephants. Moreover, better understanding p53 could help us develop targeted drug therapies in humans.

“This is an exciting development for our understanding of how p53 helps prevent the development of cancer,” explained co-author Professor Robin Fåhraeus. “In humans, the same p53 protein is responsible for deciding whether cells should stop proliferating or enter apoptosis, but how p53 makes this decision has been difficult to elucidate. The existence of multiple isoforms of p53 in elephants with different abilities to interact with MDM2 offers an exciting new approach to shed new light on the tumor suppressor activity of p53.”

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