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Inhibition of the 53BP2S‐mediated apoptosis by nuclear factor κB and Bcl‐2 family proteins
Author(s) -
Takahashi Naoko,
Kobayashi Shinya,
Kajino Shinichi,
Imai Kenichi,
Tomoda Keisuke,
Shimizu Shigeomi,
Okamoto Takashi
Publication year - 2005
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2005.00878.x
Subject(s) - biology , apoptosis , bcl 2 family , microbiology and biotechnology , genetics , cancer research , programmed cell death
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 over‐expression 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.