Gene of the Month - p53

14 May 2017
Posted by Kat Arney.

It’s time for our gene of the month - p53, also known as the Guardian of the Genome.

The story starts back in the 1970s when a British scientist called David Lane was working with his colleagues at the Imperial Cancer Research Fund (now Cancer Research UK) studying a monkey virus, known as SV40, which caused cancer in mouse cells grown in the lab.

In particular they were looking at two proteins made by the virus – known as the “large T” and “small t” antigens, believed to be the key to its cancer-causing abilities. By trawling infected cell extracts with these proteins, in the same way a fisherman might trawl the sea with a net, Lane hooked out a small protein weighing just 53 kilodaltons (that’s the unit of measurement for molecules).

Writing in their groundbreaking 1979 paper, published in the journal Nature, Lane and his boss Lionel Crawford note that “It is possible that [the mystery protein] … may normally act as a regulator of certain cellular functions related to growth control…It is of prime importance to determine the level of this … protein in [normal] cells and to see if it is induced by other carcinogenic agents.”

The human gene that encodes p53, called TP53, was found in 1984 and we now know it’s responsible for turning other genes on in response to DNA damage. You can see your own TP53 gene at work if you’ve ever been foolish enough to get sunburnt – that horrible peeling stuff is dead skin cells, killed as a result of p53 switching on a cell ‘suicide’ pathway preventing the damaged cells from turning cancerous - hence its nickname, “the guardian of the genome”. That’s great when it’s working, but the majority of cancers seem to switch off the gene or somehow inactivate the protein, effectively throwing the guardian in jail and running riot in the body.

Since its discovery, p53 is now known to be involved in a huge range of biological functions, from ageing and immunity to development in the womb. Nearly four decades on from David Lane’s first discovery, scientists are still trying to figure out exactly how it works inside cells, and how to use that knowledge to tackle cancer and other diseases.

One approach is to use drugs that can reactivate p53 in cancer cells - letting it out of prison so it can kill the rogue cells. Another approach is to specifically target and kill cells that don’t have active p53 - which should be cancer cells, rather than healthy ones. So far this is all at an experimental stage, so watch this space.

And speaking of Guardians - but of the galaxy rather than the genome - as far as I can tell, there are currently no genes named Groot or Baby Groot, so they’re still up for grabs in case you’re a geneticist in search of ideas for your latest DNA discovery.

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