Policing of oncogene activity by p53

Oncogenes, rather than DNA damage, may provide the key signal to p53 to trigger tumour suppression.

Abstract

The tumour-suppressor protein p53 provides the most important genetic defence against cancer¹ and is activated in response to DNA damage and to oncogenic signalling, both of which occur almost universally in malignant tumours. But the relative contribution of these two pathways in inducing p53-dependent protection against cancer is unclear. Here we show that p53-dependent protection against cancer is lost in mice that have been genetically manipulated so that their p53 is activated in response to DNA damage but not to oncogenic signalling. We conclude that oncogenic signalling is the critical event that elicits p53-dependent protection and that the DNA-damage stimulus is less important.