DEC1 and MIC-1

The p53 tumor suppressor is an essential barrier against cancer, which is evidenced by loss of p53 activity in the majority of human cancers and unexceptionally early onset of tumors in p53-knockout mice and human Li-Fraumeni syndrome patients. p53 is a sequence-specific transcription factor that regulates gene expression via binding to the consensus p53-responsive element (p53-RE). p53 acts as a central signaling coordinator that receives upstream signals, including DNA damage, aberrant oncogenic activity, hypoxia and ribosomal stress, and consequently activates its targets leading to downstream cellular outcomes, including cell cycle arrest, DNA repair, apoptosis and cellular senescence. However, it is not yet clear how p53 dictates a cell to survival vs. death in response to a specific stress. It has been shown that the ability of p53 to regulate target genes can be modulated by posttranslational modifications. For example, acetylation of p53 on lysine 120 by Tip60 is crucial for p53-mediated apoptosis but not cell cycle arrest. Consistently, p90, a cofactor of Tip60, is required for Tip60-dependent p53 acetylation and, thus, specifically promotes p53-mediated apoptosis. Interestingly, evidence showed that p53 activity is also regulated by binding partners that do not affect p53 modifications. For example, ASPP proteins interact with p53 and enhance the DNA binding and transactivation function of p53 on the promoters of pro-apoptotic genes, such as Bax and PIG3. Similarly, p53β preferentially enhances p53 transcriptional activity on the Bax but not p21 promoter. In addition, hCAS/ CSE1L, a factor identified in the p53 transcription complex, specifically associates with the PIG-3 promoter to induce DEC1 and MIC-1 New players of p53-dependent cell fate decision