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.
authors.affiliation: Experimental Oncology 1, CRO National Cancer Institute, Aviano 33081, Italy. spiccinin@cro.it
authors.forename: Sara
authors.initials: S
authors.lastname: Piccinin
authors.forename: Elena
authors.initials: E
authors.lastname: Tonin
authors.forename: Sara
authors.initials: S
authors.lastname: Sessa
authors.forename: Silvia
authors.initials: S
authors.lastname: Demontis
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rossi
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pecciarini
authors.forename: Lucia
authors.initials: L
authors.lastname: Zanatta
authors.forename: Flavia
authors.initials: F
authors.lastname: Pivetta
authors.forename: Alessandra
authors.initials: A
authors.lastname: Grizzo
authors.forename: Maura
authors.initials: M
authors.lastname: Sonego
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Claudio
authors.initials: C
authors.lastname: Doglioni
authors.forename: Roberta
authors.initials: R
authors.lastname: Maestro
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D056915:DNA Copy Number Variations; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C495901:TP53 protein, human; C103173:TWIST1 protein, human; C486274:TWIST2 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2