Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53.

Article Details

Citation

Golubovskaya VM, Finch R, Cance WG

Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53.

J Biol Chem. 2005 Jul 1;280(26):25008-21. Epub 2005 Apr 25.

PubMed ID
15855171 [ View in PubMed
]
Abstract

Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors and associates with multiple cell surface receptors and intracellular signaling proteins through which it can play an important role in survival signaling. A link between FAK and p53 in survival signaling has been reported, although the molecular basis of these events has not been described. In the present study, we report that FAK physically and specifically interacts with p53 as demonstrated by pull-down, immunoprecipitation, and co-localization analyses. Using different constructs of N-terminal, central, and C-terminal fragments of FAK and p53 proteins, we determined that the N-terminal fragment of FAK directly interacts with the N-terminal transactivation domain of p53. Inhibition of p53 with small interfering p53 RNA resulted in a decreased complex of FAK and p53 proteins in 293 cells, and induction of p53 with doxorubicin in normal human fibroblasts caused an increase of FAK and p53 interaction. Introduction of the FAK plasmid into p53-null SAOS-2 cells was able to rescue these cells from apoptosis induced by expression of wild type p53. In HCT 116 colon cancer cells, co-transfection of FAK plasmid with p21, MDM-2, and BAX luciferase plasmids resulted in significant inhibition of p53-responsive luciferase activities, demonstrating that FAK can reduce transcriptional activity of p53. The results of the FAK and p53 interaction study strongly support the conclusion that FAK can suppress p53-mediated apoptosis and inhibit transcriptional activity of p53. This provides a novel mechanism for FAK-p53-mediated survival/apoptotic signaling.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Focal adhesion kinase 1Q05397Details
Cellular tumor antigen p53P04637Details