FUSE binding protein1 interacts with Tumor Suppressor p53 and p53-Isoforms through their DNA Binding domain: Mapping the FBP1 binding site

Abstract

Abstract We have earlier demonstrated that a cellular factor, FUSE binding protein1 (FBP1), physically interacts and effectively suppresses the function of tumor suppressor p53 and promotes persistent HCV replication [Dixit et al. JVI 89:7905, 2015). In the present study, we demonstrate that FBP1 interacts with various naturally occurring p53-isoforms isolated from different cancers that carry large deletions at the N- and C-terminal regions but still have an intact DNA binding domain (DBD). We discovered that FBP1 specifically interacts with the DNA binding domain (DBD) of p53 and its isoforms. We further mapped the FBP1-interaction site and identified a 21-residue-long motif spanning amino acid residues 163–183 in the p53-DBD. We further confirmed that Arg175/Cys176, within this motif, is necessary for FBP1 interaction. Arg175/Cys176, located at the junction of the β4 and H1 helix of the L2 Loop, is required for the DNA binding function of p53. Occupying this site containing Arg175/Cys176 by FBP1 may block the DNA binding function of p53.