The protein, known as Bcl-xL, normally protects cells from dying. When the DNA in cells becomes damaged, Bcl-xL is modified so that it no longer keeps cells alive. But in the presence of a particular cancer gene, the usual modification of Bcl-xL following DNA damage does not occur, so cells with DNA damage are kept alive, resulting in cancer.
The discovery, described in an article in Cancer Cell (19 January), was made by Dr Rui Zhao, working in Dr Denis Alexander's research group at the Babraham Institute. Using a transgenic mouse model engineered to develop T cell lymphoma, Zhao investigated the molecular events involved in transforming a healthy cell into a malignant one.
He noticed that the change (a deamidation) in Bcl-xL that normally occurs after exposing cells to radiation no longer happened when the particular cancer gene was present.
Although the study was conducted in a T cell lymphoma model, Dr Alexander believes it is "quite likely that this mechanism could be relevant to other types of cancer as well - 24,500 people in Britain every year are diagnosed with a cancer of the blood."
Intriguingly, the cancer gene being studied at the Babraham Institute (a hyperactive tyrosine kinase) acts by a double mechanism. In the first instance, it inhibits the rapid repair of DNA damage that often occurs as cells divide, so mutations accumulate in cells containing the cancer gene. Additionally, the cancer gene prevents the cells with damaged DNA from being eliminated, so leading to cancer.
"It is quite likely," says Alexander, "that if only one of these mechanisms were taking place, there would be no cancer. Its when both occur simultaneously, the 'double-whammy', that the catastrophe happens."
Alexander's group has also shown that the critical modification of Bcl-xL, prevented by the cancer gene even before the cancer gets started, also remains blocked in tumours even when they've been exposed to reagents used in chemotherapy.
"If we could find a way of averting this blockade … then the tumour would either spontaneously die or would at least become more sensitive to chemotherapy or radiotherapy," he said.