The 7-amino-acid site in the proline-rich region of the N-terminal domain of p53 is involved in the interaction with FAK and is critical for p53 functioning

The Biochemical Journal
Vita GolubovskayaWilliam G Cance

Abstract

It is known that p53 alterations are commonly found in tumour cells. Another marker of tumorigenesis is FAK (focal adhesion kinase), a non-receptor kinase that is overexpressed in many types of tumours. Previously we determined that the N-terminal domain of FAK physically interacted with the N-terminal domain of p53. In the present study, using phage display, sitedirected mutagenesis, pulldown and immunoprecipitation assays we localized the site of FAK binding to a 7-amino-acid region(amino acids 65-71) in the N-terminal proline-rich domain of human p53. Mutation of the binding site in p53 reversed the suppressive effect of FAK on p53-mediated transactivation ofp21, BAX (Bcl-2-associated X protein) and Mdm2 (murine double minute 2) promoters. In addition, to functionally test this p53 site, we conjugated p53 peptides [wild-type (containing the wild-type binding site) and mutant (with a mutated 7-aminoacid binding site)] to a TAT peptide sequence to penetrate the cells, and demonstrated that the wild-type p53 peptide disrupted binding of FAK and p53 proteins and significantly inhibited cell viability of HCT116 p53+/+ cells compared with the control mutant peptide and HCT116 p53-/- cells. Furthermore, the TAT-p53 peptide decrease...Continue Reading

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Citations

Oct 23, 2010·Nature Reviews. Molecular Cell Biology·Margaret C FrameMichael J Eck
Jun 3, 2010·Frontiers in Bioscience (Landmark Edition)·Vita M Golubovskaya, William Cance
Jun 21, 2015·Progress in Biophysics and Molecular Biology·Katarzyna W WalkiewiczStefan T Arold
Sep 10, 2013·Surgical Oncology Clinics of North America·Vita M Golubovskaya, William G Cance
Jul 12, 2011·Microvascular Research·Noureddine ZebdaKonstantin G Birukov
Jul 3, 2009·Current Opinion in Cell Biology·Andrew P GilmoreJennefer Lindsay
Apr 12, 2015·The Journal of Surgical Research·Lauren A GilloryElizabeth A Beierle
Feb 17, 2009·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·K G FranchiniT M Marin
Jun 14, 2008·FEBS Letters·Valeria OssovskayaDusko Ilic
Jun 13, 2019·Journal of Experimental & Clinical Cancer Research : CR·Jin ZhouLiling Tang
Jul 1, 2021·Journal of Thrombosis and Haemostasis : JTH·Bal Krishan SharmaJoseph S Palumbo
May 22, 2008·Science Signaling·William G Cance, Vita M Golubovskaya

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