The TP53 gene is responsible for making a protein known as p53, which helps to protect our bodies from cancer by slowing the spread of cancerous cells. Even though p53 is a promising target for cancer treatment, the protein is not very stable and breaks down rapidly within cells. In a groundbreaking new study from Karolinska Institutet, researchers have demonstrated that a spider silk protein can stabilize and strengthen p53.
The experts explain that if a cell is lacking functional p53, it quickly becomes a cancer cell that starts to divide uncontrollably. The research suggests that adding spider silk to p53 increases its ability to kill cancer cells and keep them from spreading.
“The problem is that cells only make small amounts of p53 and then quickly break it down as it is a very large and disordered protein,” said study last author Michael Landreh. “We’ve been inspired by how nature creates stable proteins and have used spider silk protein to stabilise p53. Spider silk consists of long chains of highly stable proteins, and is one of nature’s strongest polymers.”
In the Department of Biosciences and Nutrition at Karolinska Institutet, Jan Johansson and Anna Rising use spider silk in their research. Along with Landreh, the researchers attached synthetic spider silk protein onto the human p53 protein. When the modified protein was introduced into human cells, the cells started to produce it in large quantities.
The experts found that the new protein was more stable and potent than unmodified p53.
Electron microscopy, computer simulations, and mass spectrometry revealed that the spider silk seemed to add structure to the disordered sections of p53.
Going forward, the experts want to gain a more detailed understanding of the structure of p53, and how its various parts interact to prevent cancer. The researchers will also investigate how the more potent protein they have created with spider silk may affect cells.
“Creating a more stable variant of p53 in cells is a promising approach to cancer therapy, and now we have a tool for this that’s worth exploring,” said study co-author Sir David Lane. “We eventually hope to develop an mRNA-based cancer vaccine, but before we do so we need to know how the protein is handled in the cells and if large amounts of it can be toxic.”
Sir David Lane is one of the scientists who first discovered the p53 protein, which is referred to as the “guardian of the genome” due to its ability to stop cells with DNA damage from turning into cancer cells. Mutations of the TP53 gene are present in roughly half of all cancer tumors, representing the most common genetic change in cancer.
The study is published in the journal Structure.
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By Chrissy Sexton, Earth.com Staff Writer