Figure 1
Multiple mechanisms of mutant p53 GOF. (a) Mutant p53 binds to transcription factors (TF) and enhances the transactivation of target genes. (b) Mutant p53 binds various transcription factors and subverts their binding to DNA motifs at the promoters of target genes, leading to reduced expression of target genes. (c) Mutant p53 (light blue circle) modifies the architecture of chromatin by binding and activation of chromatin-modifying enzymes (orange triangle), resulting in enhanced gene expression within spans of accessible chromatin. In this mechanism of mutant p53 GOF, genes occupying entire regions of chromatin may be exposed to existing transcriptional machinery, resulting in gene expression in which gene promoters are not directly bound by mutant p53. Such effects of mutant p53 would not be evident in assays that detect the occupancy of mutant p53 within gene promoters such as ChIP-seq
