"We all have p53 inside us. We all have a p53 gene and this p53 gene makes p53 protein. Normally your p53 levels are low but if your DNA gets damaged your p53 increases, damaged cells can be allowed to repair or if the damage is severe they can be killed off by apoptosis. You have so many cells that it doesn’t matter if a few badly damaged ones die off. It is far better to lose a damaged cell than have it grow and develop into a cancerous tumour.
So just what does p53 protein do? p53 protein is a “transcription factor” which means it binds to genes. This can turn genes on “activate” them or it can turn genes off and “repress” them. p53 can do both, it can turn some genes on and some genes off.
A recent paper in the August 25 edition of the journal PNAS (Proceedings of the National Academy of Sciences of the United States of America) explains how scientists have discovered a specific genetic sequence that will bind p53 and turn off a gene. I’m pleased to say the paper is open access so anyone can read it, it is called “Redefining the p53 response element” and the research was carried out in Singapore.
If you didn’t do biology at school, this table might help you understand the details:
| Name | What is it? | Example |
DNA | deoxyribonucleic acid | A code you inherit from your parents |
gene | a short bit of DNA that codes for proteins | e.g. insulin,adrenaline, oestrogen, p53 |
gene sequence | 4 chemicals ATCG in a specific order that code for a protein | ATCCGGTATCCCAT |
Protein sequence | 20 chemicals that make up protein | alanine, serine, tryptophan, leucine |
So what if you know an off sequence? Well the human genome has been sequenced (you can look at it here, click on the chromosomes on the right hand side if your are interested). We know the sequence of the 30,000 odd genes needed to make a human, we can now look through that list and find out which genes are turned off by p53. In the PNAS paper the authors describe 162 different genes that are controlled by p53. 123 of these genes are turned on by p53 and 39 of these genes are turned off by p53, the scientists can predict what will happen by looking at the sequence of any gene.
What did the scientists do? In a lab they made two bits of DNA (”constructs”). One was a gene called p21 that we know is turned on by p53 and one was a gene called Lasp1 that is turned off by p53. They then changed the DNA, one bit at a time to see what happened. This is many years worth of research, it sounds simple but it takes a long time to do in the lab.
They discovered that a DNA sequence with AT, AA or TT meant that the gene would be turned on by p53 and that the DNA sequence CG, TG, CC, GC and CA meant the gene would be turned off by p53.
Why is this important?p53 does not work properly in over half of all human tumours. Lots of charities and drug companies are trying to develop new drugs either to restore damaged p53 or to activate the p53 pathway in cancer cells and cause them to die. To learn more about this watch this emedtv video with David Lane, one of the first scientists to discover p53 30 years ago.
What is so difficult about this research?Trying to find things that are turned off is a lot harder than trying to find things that are turned on! For example, if I was to send you into a dark room and ask you to find 4 lights, all of which were turned on, it would be an easy thing to do. If, however, I was to send you into a pitch dark room and ask you to find 4 lights (all of which were turned off) you’d find it a lot harder. It’s the same with genes, it’s easier to find things that are turned on than things that are turned off. This research paper is important because it give us a way of finding more genes that are turned off by p53 and this will help us to understand what goes wrong when p53 doesn’t work.
I have cancer now, does this research help me?This research was carried out in cells in a laboratory, grown in a dish and the findings don’t alter any of the standard cancer treatments like chemo, radiotherapy or surgery. However, this research give us a better understanding of how p53 works which will hopefully lead to better treatments in the future.
Where can I find out more?
Cancer Research UK Press Release - Singapore team shed light on tumour suppressor gene
Science News – Widely sought molecular key to understanding p53
Singapore Immunology Network – SiGN – REN Ee Chee"
What did the scientists do? In a lab they made two bits of DNA (”constructs”). One was a gene called p21 that we know is turned on by p53 and one was a gene called Lasp1 that is turned off by p53. They then changed the DNA, one bit at a time to see what happened. This is many years worth of research, it sounds simple but it takes a long time to do in the lab.
They discovered that a DNA sequence with AT, AA or TT meant that the gene would be turned on by p53 and that the DNA sequence CG, TG, CC, GC and CA meant the gene would be turned off by p53.
Why is this important?p53 does not work properly in over half of all human tumours. Lots of charities and drug companies are trying to develop new drugs either to restore damaged p53 or to activate the p53 pathway in cancer cells and cause them to die. To learn more about this watch this emedtv video with David Lane, one of the first scientists to discover p53 30 years ago.
What is so difficult about this research?Trying to find things that are turned off is a lot harder than trying to find things that are turned on! For example, if I was to send you into a dark room and ask you to find 4 lights, all of which were turned on, it would be an easy thing to do. If, however, I was to send you into a pitch dark room and ask you to find 4 lights (all of which were turned off) you’d find it a lot harder. It’s the same with genes, it’s easier to find things that are turned on than things that are turned off. This research paper is important because it give us a way of finding more genes that are turned off by p53 and this will help us to understand what goes wrong when p53 doesn’t work.
I have cancer now, does this research help me?This research was carried out in cells in a laboratory, grown in a dish and the findings don’t alter any of the standard cancer treatments like chemo, radiotherapy or surgery. However, this research give us a better understanding of how p53 works which will hopefully lead to better treatments in the future.
Where can I find out more?
Cancer Research UK Press Release - Singapore team shed light on tumour suppressor gene
Science News – Widely sought molecular key to understanding p53
Singapore Immunology Network – SiGN – REN Ee Chee"
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