The new WEHI-TV animation visualises discoveries from more than 40 years of research to explain how the tumour suppressor protein p53 normally prevents cancer-causing changes in cells. More than half of human cancer cases involve faulty p53.
The animation was produced by WEHI.TV biomedical animator Ms Etsuko Uno, who worked closely with WEHI cancer researchers Professor Andreas Strasser and Dr Gemma Kelly to ensure the animation’s scientific accuracy.
In our bodies, p53 is an essential controller of cell division, cell death and DNA repair, ensuring that healthy cells can divide as needed, but forcing cells with damaged DNA to stop dividing and undergo repair – or die, if the damage is too severe. These processes are critical for maintaining good health; cancer is caused by damaged cells being allowed to persist and grow uncontrollably.
Cancer researcher Dr Gemma Kelly, who narrated the animation, said more than half of human cancers carry defects in p53.
“The most frequently mutated gene in human cancer is p53 – and it is, I think, the most important ‘tumour suppressor’ protein. Mutations of the p53 gene are particularly common in several prevalent cancer types with poor prognosis, including lung cancer, ovarian cancer and pancreatic cancer,” she said.
“Despite 40 years of intense research into p53, there is still a lot to learn about how this tumour suppressor works, in order to develop better therapies for cancers that have defective p53.”
The new WEHI.TV animation was created to clearly explain the latest knowledge about p53, said its creator Ms Etsuko Uno.
“Working closely with our researchers, I was able to produce very complex pictures of p53 functioning within cells, which reflect the most up-to-date data about this tumour suppressor,” she said.
“This has been one of the most challenging proteins I have illustrated, because – unlike most other proteins I have tackled – this protein is largely unstructured. WEHI’s structural biology researchers provided valuable guidance on how to accurately depict it.”
“To create the detailed molecular shapes and movements, we turned to technologies used to make computer games, using a production software called Unity,” Ms Uno said.
The new animation demonstrates how p53 responds to DNA damage in cells, ‘turning on’ the production of proteins that can repair the damage. It also stops the cells dividing, to allow time for this repair and prevent errors in genes being transmitted to new cells. However, if the damage is too severe, p53 delivers its final blow, directing the production of ‘cell death’ proteins that trigger the cell’s demise, by a programmed cell death process called apoptosis.
The animation also explains how malfunctions in p53 can lead to cancer development, by not adequately repairing DNA damage within cells.
Cancer researcher Professor Andreas Strasser said the animation provided a vivid and accessible explanation of how tumour suppressors within our cells work to prevent cancer developing. “It’s a wonderful educational resource, which clearly explains how p53 protects us from cancer,” he said.
“I am thrilled to see how it incorporates the latest discoveries about how p53 functions – including discoveries made by my own research group – incorporated in a dynamic and scientifically accurate way.”
Professor Strasser and Dr Kelly’s research into p53 has received substantial support from the Dyson Bequest, The Craig Perkins Cancer Research Foundation, the National Health and Medical Research Council, the Victorian Cancer Agency, Cancer Council Victoria, the Leukemia Foundation of Australia, the Redstone Foundation Bequest and the Victorian Government.
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