In response to oncogenic stress, the tumour suppressor ARF activates the p53 protein. ARF protein is highly stable in most human cell lines, so it has been thought that ARF activation occurs mainly at the level of transcription. Here, however, ARF is shown to be unstable in normal human cells but stable in cancer cells, through a transcription-independent mechanism. A ubiquitin ligase for ARF is identified and shown to promote ARF degradation in normal cells. This activity is prevented in cancer cells, stabilizing ARF.
- Delin Chen
- Jing Shan
- Wei Gu
