A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53 degradation

Cancer Cell. 2012 Sep 11;22(3):404-15. doi: 10.1016/j.ccr.2012.08.003.


Twist proteins have been shown to contribute to cancer development and progression by impinging on different regulatory pathways, but their mechanism of action is poorly defined. By investigating the role of Twist in sarcomas, we found that Twist1 acts as a mechanism alternative to TP53 mutation and MDM2 overexpression to inactivate p53 in mesenchymal tumors. We provide evidence that Twist1 binds p53 C terminus through the Twist box. This interaction hinders key posttranslational modifications of p53 and facilitates its MDM2-mediated degradation. Our study suggests the existence of a Twist box code of p53 inactivation and provides the proof of principle that targeting the Twist box:p53 interaction might offer additional avenues for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • DNA Copy Number Variations
  • Epithelial-Mesenchymal Transition
  • Humans
  • Mice
  • Mice, Nude
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Proto-Oncogene Proteins c-mdm2 / biosynthesis
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • RNA Interference
  • RNA, Small Interfering
  • Repressor Proteins / metabolism
  • Sarcoma / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Twist-Related Protein 1 / biosynthesis
  • Twist-Related Protein 1 / genetics
  • Twist-Related Protein 1 / metabolism*


  • Nuclear Proteins
  • RNA, Small Interfering
  • Repressor Proteins
  • TP53 protein, human
  • TWIST1 protein, human
  • TWIST2 protein, human
  • Tumor Suppressor Protein p53
  • Twist-Related Protein 1
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2