Research Says Chain Reaction is Required to Prevent Tumor Formation

In contrast to "normal" cells, the cell cycle of tumour cells is out of control, causing the anarchic proliferation of cells, the cause of cancer. The cells become immortal, thus causing significant deregulations in the body. A few years ago, researchers proved that the protein p53 gene is inactive in half of all human cancers. The p53 coding gene was classified as a tumour-suppressing gene. Scientists suggested a new hypothesis: if this gene were reactivated, this uncontrolled cell activity, responsible for the formation of cancer tumours, could be prevented. However, they would later discover that p53 is itself regulated by another factor: protein Mdm2. They then thought they had discovered a means to reactivate p53.

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Today, Robin Farhaeus and his collaborators have provided a new element in the understanding of carcinogenesis mechanisms: the involvement of protein kinase ATM in the p53 regulation via Mdm2. "Following DNA damage, Mdm2 is required to activate p53 and this may occur through the intervention of the ATM kinase protein" explains Robin Farhaeus, Inserm Research Director.

To complete the demonstration, the researchers highlighted the chain of events that triggers p53 activation. Mdm2 activation is caused by phosphorylation through the ATM kinase protein, which is itself activated in the event of cell stress. This phosphorylation of Mdm2 is crucial for the transition from a negative p53 regulator state to a positive p53 regulator state (thus encouraging its interaction with p53 ARN messenger to cause translation). This leads to an increased quantity of p53 in the cell.

This study improves understanding of how the respective regulation of p53 and Mdm2 are organised in response to damaged DNA. Better understanding of specific molecular mechanisms at work during cell stress may help create new therapeutic approaches to cancer.



Source: Eurekalert