Role of p53/FAK association and p53Ser46 phosphorylation in staurosporine-mediated apoptosis: wild type versus mutant p53-R175H.
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-p53(Ser46)) 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.
Fanucchi
Stephanie
S
School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa.
Veale
Robin B
RB
D019943:Amino Acid Substitution; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D010766:Phosphorylation; D021381:Protein Transport; D012694:Serine / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016159:Tumor Suppressor Protein p53; D012694:Serine; D051417:Focal Adhesion Kinase 1; D053148:Caspase 3; D019311:Staurosporine