Spider’s thread strengthens cancer-inhibiting protein Spider’s thread stops cancer

The p53 protein plays a key role in the body’s defense against cancer, among other things by detecting and preventing genetic changes that can lead to cancer. If a cell lacks functional p53, it quickly transforms into a cancer cell that begins dividing uncontrollably. Therefore, attempts are underway around the world to develop cancer therapies that target p53 in different ways.

The problem is that cells make very little p53 and then break it down quickly, because it’s a very large and informal protein, says Michael Landrae, a researcher in the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet.

Now, researchers at Karolinska Institutet have found a different way to stabilize the protein and thus make it more effective. By attaching a piece of spiderweb protein to p53, they showed that they could form a more stable protein while also increasing the ability to kill cancer cells.

Spider web stabilizes cancer-killing protein

We drew inspiration from how nature creates stable proteins and uses spiderweb protein to stabilize p53. Spider web is made of long chains of highly stable proteins and is one of the strongest polymers in nature.

In collaboration with, among others, Jan Johansson and Anna Rising in KI’s Department of Biosciences and Nutrition, who use spiderwebs in their research, the researchers tested binding of a small piece of the synthetic spider web protein to the human p53 protein. And when they then added it to the cells, they found that the cells started producing it in large quantities. It was also found that the new protein is more stable than the regular p53 protein and has an improved ability to kill cancer cells.

Using electron microscopy, computer simulations and mass spectrometry, they were able to show that this is probably due to the fact that the cobweb part manages to form the amorphous parts of p53.

The researchers now plan to study in detail the protein’s structure and how the different parts of it work together to prevent cancer. They will also discover how cells are affected by the new functional p53 protein and how well they tolerate the spiderweb portion of the protein.

Creating a more stable variant of p53 in cells is a promising approach to treating cancer, and now we have a tool for this that’s worth exploring. In the long term, we hope to be able to move forward with the development of an mRNA-based cancer vaccine, but before that we need to know how the protein is handled in cells and whether it is toxic in large quantities, for example, says Sir David Lane, Professor The first at Karolinska Institutet.

Sir David Lane was one of those who discovered p53 in the late 1970s. P53 is called the guard of the genome because it can prevent cells with DNA damage from developing into cancerous cells. Mutations in the p53 gene are found in about half of all carcinoid tumors, making it the most common genetic alteration in cancer.

“Understanding more about p53 and trying to take advantage of this property in tumors for clinical benefits has become the topic of my research,” says David Lane, professor of tumor suppressor biology in the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. By understanding what p53 does, we can also understand what is essential in cancer. The film is 1 minute 23 seconds long.

The study is a collaboration between researchers at Karolinska Institutet, KTH, Stockholm University and A*STAR (Agency for Science, Technology and Research) in Singapore.

Scientific material:

Spindle and filament machinery de-blocks p53 translation by modulating N-terminal disruption (Margit Kaldmay, Thibo Fuselman, Xueying Zhong, Dilraj Lama, Gefei Chen, Mihkel Saluri, Nina Kronqvist, Jia Wei Siau, Aik Seng Ng, Fred J. Ilag, Venla A. Vananen, Saikiran Sedembe, Marie Arsenian-Henrikson, Roman A. (.Zubarev, Lennart Nelson, Philip J.P. Quick, Anna Rising, Axel Abelin, Nicholas Fritz, Jan Johansson, David B. Lin, and Michael Landre)structure.