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.
Source : A "Twist box" Code
of p53 Inactivation: Twist box:p53 Interaction Promotes p53 Degradation.
Piccinin S, Tonin E, Sessa S, Demontis S, Rossi S, Pecciarini L, Zanatta L,
Pivetta F, Grizzo A, Sonego M, Rosano C, Dei Tos AP, Doglioni C, Maestro R.
Cancer Cell. 2012 Sep 11;22(3):404-15.
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