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.
School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg 2050, South Africa.
Stephanie
S
Fanucchi
Robin B
RB
Veale
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