A high-throughput loss-of-function screening identifies novel p53 regulators

The p53 protein is a sequence-specific transcription factor that plays a crucial role in tumor suppression by inducing apoptosis or cell cycle arrest in response to cellular damage. To identify novel proteins involved in the regulation of p53 transcriptional activity we have performed a large scale RNA interference-based screen. We have identified four genes previously unknown to be involved in modulating p53 activity (GAS41, RPS6K4, RUNDC1 and CRMP-2). The interference of each of these four genes resulted in the upregulation of p53 transcriptional activity and, conversely, their overexpression resulted in the inhibition of p53 target promoters and p53-mediated apoptosis. These observations suggest a role for these genes as p53 inhibitors and imply that they may have oncogenic activity.