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FAK and p53 protein interactions
Vita M Golubovskaya1, William G Cance
1Department of Surgical Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. Vita.Golubovskaya@roswellpark.org
Abstract:
Focal Adhesion Kinase plays a major role in cell adhesion, motility, survival, proliferation, metastasis, angiogenesis and lymphangiogenesis. In 2004, we have cloned the promoter sequence of FAK and found that p53 inhibits its activity (BBA, v. 1678, 2004). In 2005, we were the first group to show that FAK and p53 proteins directly interact in the cells (JBC, v. 280, 2005). We have shown that FAK and p53 proteins interact in the cytoplasm and in the nucleus by immunoprecipitation, pull-down and confocal microscopy assays. We have shown that FAK inhibited activity of p53 with the transcriptional targets: p21, Bax and Mdm-2 through protein-protein interactions. We identified the 7 amino-acid site in p53 that is involved in interaction with FAK protein. The present review will discuss the interaction of FAK and p53 proteins and discuss the mechanism of FAK-p53 loop regulation: inhibition of FAK promoter activity by p53 protein and also inhibition of p53 transcriptional activity by FAK protein.
Insights
Focal Adhesion Kinase (FAK) and p53 protein interaction regulates cell functions. This review details how FAK and p53 mutually inhibit each other
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Focal Adhesion Kinase (FAK) is crucial for cell adhesion, motility, and cancer progression.
- The tumor suppressor protein p53 regulates cell cycle and apoptosis.
- Previous work established FAK promoter regulation by p53 and direct FAK-p53 interaction.
Purpose of the Study:
- To review the intricate interaction between FAK and p53 proteins.
- To elucidate the regulatory feedback loop between FAK and p53.
- To discuss the molecular mechanisms underlying FAK-p53 cross-regulation.
Main Methods:
- Cloning of the FAK promoter sequence.
- Immunoprecipitation, pull-down assays, and confocal microscopy to confirm protein interactions.
- Identification of the specific amino acid site in p53 involved in FAK interaction.
Main Results:
- FAK and p53 proteins directly interact within cellular cytoplasm and nucleus.
- FAK inhibits p53 transcriptional activity on targets like p21, Bax, and Mdm-2.
- A 7-amino acid site on p53 mediates its interaction with FAK.
Conclusions:
- The FAK-p53 interaction forms a critical regulatory loop.
- p53 inhibits FAK promoter activity, while FAK inhibits p53 transcriptional activity.
- Understanding this interplay is vital for comprehending cell signaling in cancer.
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