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Role of p53/FAK association and p53 phosphorylation in staurosporine-mediated apoptosis: Wild type versus mutant p53-R175H |
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| Authors: | Stephanie Fanucchi |
| Institution: | School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa |
| Abstract: | A novel survival role of focal adhesion kinase (FAK) that involves its nuclear translocation and direct association with p53 has been demonstrated. Here we examined the relationship between the p53/FAK interaction and Ser46 phosphorylation of p53 (p-p53Ser46) in the apoptotic regulation of human esophageal squamous cell carcinoma (HOSCC) cell lines, expressing either wild type (wt) p53 or mutant (mt) p53-R175H. In contrast to the wt p53 cell lines, the mt p53-R175H cell line was resistant to staurosporine (STS)-mediated detachment and caspase-3 activation. Furthermore, despite the resistance of mt p53-R175H to Ser46 phosphorylation, both wt and mt HOSCC cells translocate FAK into the nucleus and maintain the p53/FAK interaction post STS treatment. These findings provide unique insight into how tumor cells harboring the R175H mutant may resist chemotherapeutic intervention.Structured summaryMINT-7294020: FAK (uniprotkb:Q05397) physically interacts (MI:0915) with p53 (uniprotkb:P04637) by anti-bait coimmunoprecipitation (MI:0006) |
| Keywords: | DMEM Dulbecco&rsquo s modified eagles medium DMSO dimethyl sulfoxide ECM extracellular matrix FAK focal adhesion kinase FCS fetal calf serum FITC fluoroscine isothiocyanate HRP horseradish peroxidase HOSCC human esophageal squamous cell carcinoma mt mutant RIPA radioimmunoprecipitation assay SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis STS staurosporine TUNEL terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling pFAKTyr397 Tyr 397 phosphorylation of FAK p-p53Ser46 Ser46 phosphorylation of p53 wt wild type |
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