To repress or not to repress: this is the guardian's question.

p53 is possibly the most central tumor suppressor gene of our cells, integrating stress signals to activate a transcriptional program responsible for maintaining cellular homeostasis. Many of the downstream effects of p53 are a consequence of its activity as a transcription factor, resulting in the induction of multiple target genes. In addition to gene activation, however, gene repression is an essential part of the p53 cellular response. Despite extensive research efforts towards the elucidation of p53 functions, the molecular mechanisms and biological consequences of gene repression by p53 have not been studied extensively. We review our current knowledge of the mechanisms and biological consequences of p53 repression, with special attention to recently discovered mechanisms of repression that involve non-coding RNA molecules, an emerging aspect of regulation in the p53 cellular network.