A "Twist box" Code of p53 Inactivation: Twist box:p53 Interaction Promotes p53 Degradation

Sara Piccinin, Elena Tonin, Sara Sessa, Silvia Demontis, Sabrina Rossi, Lorenza Pecciarini, Lucia Zanatta, Flavia Pivetta, Alessandra Grizzo, Maura Sonego, Camillo Rosano, Angelo Paolo Dei Tos, Claudio Doglioni, Roberta Maestro

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)404-415
Number of pages12
JournalCancer Cell
Volume22
Issue number3
DOIs
Publication statusPublished - Sep 11 2012

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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