A Special Gene in Elephants May Hold the Key to Eradicating Cancers

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Despite their enormous size and long lives, elephants are surprisingly cancer-resistant, which is why their DNA could hold the answer to avoiding cancers.

A team of scientists from seven different research institutions has employed bioinformatic modeling to examine the molecular connections of the p53 protein, which is known to defend the body against cancers, according to a press release by the University of Oxford.

The researchers revealed how 20 different molecules unique to elephants are triggered for greater sensitivity and responsiveness against carcinogenic circumstances, according to research published in Molecular Biology and Evolution. With further exploration, this could have numerous implications for cancer treatments in humans.

Elephant genes and cancer

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

However, both genetic and environmental factors have an impact on the quantity of mutations and the quality of repairs. Ageing, stress, unhealthy living conditions, and toxic substances can all speed up the pace of mutation. Cancer develops when cells divide uncontrolled and invade neighboring tissues, and the tumors caused by the accumulation of gene mutations grow at risk with age.

However, when it comes to elephants, which are notorious for their massive bodies and human-like life expectancy, they appear to defy this trend.

Tumours caused by the accumulation of gene mutations grow in risk with age, however elephants appear to defy this trend. In fact, less than five percent of elephants are predicted to die from cancer, instead of up to 25 percent in humans. According to scientists, this resistance is attributed to elephants' 20 copies of the p53 gene, as opposed to the single seen in other mammals.

P53: "The guardian of the genome"

In case you didn't know, p53 is important in controlling DNA repairing pathways and suppressing uncontrolled cell growth. When DNA is damaged, the protein activates and aids in the orchestration of a response that halts DNA replication and fixes any incorrect copies of the cell.

The p53 repair activity is unnecessary in duplicated cells with undamaged DNA and is inhibited by another protein, the oncogene MDM2 E3 ubiquitin ligase. The elephant may have 40 alleles from 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 from a single gene. 

In the new study, the researchers discovered crucial discrepancies in the initial interaction between the elephant's multiple p53 isoforms and the MDM2, thanks to biochemical studies and computer simulations.

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

"This is an exciting development for our understanding of how p53 contributes to preventing cancer development," co-author Professor Robin Fåhraeus explained. "In humans, the same p53 protein is responsible for deciding if cells should stop proliferating or go into apoptosis, but how p53 makes this decision has been difficult to elucidate. The existence of several p53 isoforms in elephants with different capacities to interact with MDM2 offers an exciting new approach to shed new light on p53’s tumor suppressor activity."

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