Mutant p53 gain of function: the NF-Y connection.

The molecular mechanisms underlying mutant p53 gain of function are becoming increasingly complex. In this issue of Cancer Cell, Di Agostino et al. identify the heterotrimeric transcription factor NF-Y as an interacting partner of mutant p53. They show that mutant p53/NF-Y complexes bind to NF-Y target promoters and recruit p300 in response to DNA damage, resulting in aberrant transactivation of NF-Y target genes and cell cycle deregulation. These data thereby implicate transcriptional activation by mutant p53 as a key mechanism responsible for its oncogenic activity.