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Updated: May 22, 2026
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response
Jenny Fung Ling Chau1, Deyong Jia, Zhongfeng Wang
1The Institute of Molecular and Cell Biology, Singapore 138673.
Nature Communications
|May 17, 2012
Summary
The BMP-Smad1 pathway regulates DNA damage response and cell survival by interacting with p53. Dysregulation of this pathway contributes to cancer development.
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- DNA damage and cellular responses are crucial in aging and cancer.
- The integration of environmental cues into DNA damage responses is not fully understood.
- The BMP-Smad1 pathway is vital for development and tissue maintenance.
Purpose of the Study:
- To investigate the role of the BMP-Smad1 pathway in DNA damage response.
- To elucidate the molecular mechanisms linking BMP-Smad1 signaling to oncogenesis.
- To explore the connection between BMP-Smad1 pathway dysregulation and cancer.
Main Methods:
- Investigated the effect of genotoxic stress on the BMP-Smad1 pathway.
- Examined the interaction between phosphorylated Smad1, p53, and Mdm2.
- Analyzed Smad1 phosphorylation and mutations in human cancer samples.
Main Results:
- Genotoxic stress induces ATM-dependent phosphorylation of Smad1 at S239.
- Phosphorylated Smad1 disrupts its interaction with PPM1A, enhancing Smad1 activity.
- Smad1 interacts with p53, inhibiting Mdm2-mediated p53 degradation and regulating cell fate.
- Altered Smad1 S239 phosphorylation and mutations were found in esophageal and gastric cancers.
Conclusions:
- The BMP-Smad1 pathway is a novel component of the DNA damage response via the ATM-p53 axis.
- Loss-of-function mutations or dysregulation in the BMP-Smad1 pathway can lead to tumorigenesis.
- This pathway represents a potential target for understanding and treating cancers associated with DNA damage response defects.
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