TY - JOUR
T1 - A "Twist box" Code of p53 Inactivation
T2 - Twist box:p53 Interaction Promotes p53 Degradation
AU - Piccinin, Sara
AU - Tonin, Elena
AU - Sessa, Sara
AU - Demontis, Silvia
AU - Rossi, Sabrina
AU - Pecciarini, Lorenza
AU - Zanatta, Lucia
AU - Pivetta, Flavia
AU - Grizzo, Alessandra
AU - Sonego, Maura
AU - Rosano, Camillo
AU - Tos, Angelo Paolo Dei
AU - Doglioni, Claudio
AU - Maestro, Roberta
PY - 2012/9/11
Y1 - 2012/9/11
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84866047749&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2012.08.003
DO - 10.1016/j.ccr.2012.08.003
M3 - Article
C2 - 22975381
AN - SCOPUS:84866047749
VL - 22
SP - 404
EP - 415
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 3
ER -