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Published on: December 27, 2016
p73 supports cellular growth through c-Jun-dependent AP-1 transactivation
Faina Vikhanskaya1, Wen Hong Toh, Iqbal Dulloo
1Laboratory of Molecular Carcinogenesis, National Cancer Centre, 11 Hospital Drive, Singapore 169610, Singapore.
Nature Cell Biology
|May 15, 2007
Summary
The tumor suppressor p73 supports cellular growth by increasing AP-1 transcriptional activity. This protein synergizes with c-Jun to promote cell survival and upregulates cyclin D1, a key gene for cell proliferation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cellular Biology
Background:
- The role of p73 overexpression in human cancers is not well understood.
- p73 is a structural and functional homologue of the tumor suppressor p53.
- Understanding p73's function is crucial for cancer therapy development.
Purpose of the Study:
- To investigate the role of p73 in cellular growth and proliferation.
- To elucidate the molecular mechanisms by which p73 influences cellular processes.
- To determine the relationship between p73, AP-1 activity, and cancer cell survival.
Main Methods:
- Gene silencing and overexpression experiments to assess p73 function.
- Analysis of AP-1 transcriptional activity and target gene expression (e.g., cyclin D1).
- Chromatin immunoprecipitation and electrophoretic mobility shift assays to study protein-DNA interactions.
Main Results:
- p73 overexpression alone suppresses growth, but synergizes with c-Jun to promote cell survival.
- Silencing p73 compromises cellular proliferation and reduces cyclin D1 expression.
- p73 enhances c-Jun-dependent AP-1 transcriptional activity by regulating c-Jun phosphorylation and Fra-1 expression.
Conclusions:
- p73 plays a novel role in supporting cellular growth by augmenting AP-1 transcriptional activity.
- p73's interaction with c-Jun and regulation of AP-1 are critical for cell survival and proliferation.
- These findings reveal a new mechanism by which p73 contributes to cancer development.
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