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Updated: May 18, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53 degradation
Sara Piccinin1, Elena Tonin, Sara Sessa
1Experimental Oncology 1, CRO National Cancer Institute, Aviano 33081, Italy. spiccinin@cro.it
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.
Insights
Twist1 protein inactivates p53 tumor suppressor in sarcomas via a novel mechanism. Targeting the Twist box interaction with p53 may offer new cancer treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Twist proteins are implicated in cancer development and progression.
- The precise mechanisms by which Twist proteins exert their functions are not fully understood.
- Understanding Twist protein roles is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To investigate the role of Twist1 in sarcoma development.
- To elucidate the mechanism by which Twist1 influences p53 tumor suppressor activity.
- To explore the potential of targeting the Twist1-p53 interaction for cancer treatment.
Main Methods:
- Investigated Twist1 function in mesenchymal tumors.
- Analyzed the interaction between Twist1 and p53.
- Assessed the impact of Twist1 on p53 posttranslational modifications and degradation.
- Evaluated the potential of targeting the Twist box:p53 interaction.
Main Results:
- Twist1 inactivates p53 in mesenchymal tumors as an alternative to TP53 mutation or MDM2 overexpression.
- Twist1 binds to the C-terminus of p53 via its Twist box domain.
- This interaction inhibits critical p53 posttranslational modifications.
- Twist1 binding facilitates MDM2-mediated degradation of p53.
- Evidence suggests a 'Twist box code' for p53 inactivation.
Conclusions:
- Twist1 plays a significant role in p53 inactivation in sarcomas.
- The Twist box:p53 interaction represents a novel mechanism of tumor suppression.
- Targeting this interaction could provide new therapeutic strategies for cancers involving Twist1.
- Further research into the Twist box code could reveal broader implications for cancer therapy.
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