Twist and p53 reciprocally regulate target genes via direct interaction

Oncogene. 2008 Sep 18;27(42):5543-53. doi: 10.1038/onc.2008.176. Epub 2008 May 26.


Twist is basic helix-loop-helix transcription factor that binds to E-boxes in gene promoters. Twist possesses an oncogenic function by interfering with the tumor suppressor function of p53. Using a membrane pull-down assay, we found that Twist directly interacts with p53 and that this interaction underlies the inhibitory effects on p53 target gene expression. Twist interacted with the DNA-binding domain of p53 and suppressed the DNA-binding activity of p53. Transcriptional activation of the p21 promoter by p53 was significantly repressed by the expression of Twist. On the other hand, p53 interacted with the N-terminal domain of Twist and repressed Twist-dependent YB-1 promoter activity. Importantly, we found that p53-dependent growth suppression was canceled by the expression of either Twist or YB-1. Thus, our data suggest that Twist inhibits p53 function via a direct interaction with p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Promoter Regions, Genetic
  • Tumor Suppressor Protein p53 / physiology*
  • Twist-Related Protein 1 / physiology*
  • Y-Box-Binding Protein 1


  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • DNA-Binding Proteins
  • Nuclear Proteins
  • TWIST1 protein, human
  • Tumor Suppressor Protein p53
  • Twist-Related Protein 1
  • Y-Box-Binding Protein 1
  • YBX1 protein, human
  • DNA