Author/Authors :
Piccinin، نويسنده , , Sara and Tonin، نويسنده , , Elena and Sessa، نويسنده , , Sara and Demontis، نويسنده , , Silvia and Rossi، نويسنده , , Sabrina and Pecciarini، نويسنده , , Lorenza and Zanatta، نويسنده , , Lucia and Pivetta، نويسنده , , Flavia and Grizzo، نويسنده , , Alessandra and Sonego، نويسنده , , Maura and Rosano، نويسنده , , Camillo and Tos، نويسنده , , Angelo Paolo Dei and Doglioni، نويسنده , , Claudio and Maestro، نويسنده , , Roberta، نويسنده ,
Abstract :
Summary
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.
