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

doi:10.1016/j.ccr.2012.08.003

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 journal › Article › peer-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 language	English
Pages (from-to)	404-415
Number of pages	12
Journal	Cancer Cell
Volume	22
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2012.08.003
Publication status	Published - Sep 11 2012

ASJC Scopus subject areas

Cancer Research
Cell Biology
Oncology

Access to Document

10.1016/j.ccr.2012.08.003

Cite this

@article{56eee0cc1cc84661bef90892f88e665e,

title = "A {"}Twist box{"} Code of p53 Inactivation: Twist box:p53 Interaction Promotes p53 Degradation",

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.",

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

year = "2012",

month = sep,

day = "11",

doi = "10.1016/j.ccr.2012.08.003",

language = "English",

volume = "22",

pages = "404--415",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "3",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84866047749&partnerID=8YFLogxK

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 -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this