Inhibition of the 53BP2S-mediated apoptosis by nuclear factor κB and Bcl-2 family proteins

Abstract

The p53 binding protein 2 (53BP2) has been identified independently as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor κB (NF-κB). It was demonstrated that overexpression of 53BP2 (renamed as 53BP2S) induces apoptotic cell death. In this study we explored the effect of NF-κB activation elicited by a physiological NF-κB inducer, interleukin-1β (IL-1β), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis. We found that both NF-κB activation and Bcl-2 family proteins could prevent the 53BP2S-mediated depression of mitochondrial transmembrane potential, activation of caspase-9, cleavage of poly ADP ribose polymerase (PARP), and cell death. These observations suggested that 53BP2S/Bbp and its directly or indirectly interacting proteins might play crucial roles in the regulation of apoptosis and contribute to carcinogenesis. It is also suggested that 53BP2S/Bbp induces apoptosis through the mitochondrial death pathway presumably by counteracting the actions of anti-apoptotic Bcl-2 family proteins. The regulatory network of the 53BP2S-mediated apoptosis cascade including its interacting proteins is discussed. © Blackwell Publishing Limited.