Inhibition of the 53BP2S-mediated apoptosis by nuclear factor kappaB and Bcl-2 family proteins.
The p53 binding protein 2 (53BP2) has been identified independently as the interacting protein to p53, Bcl-2, and p65 subunit of nuclear factor kappaB (NF-kappaB). It was demonstrated that over-expression of 53BP2 (renamed as 53BP2S) induces apoptotic cell death. In this study we explored the effect of NF-kappaB activation elicited by a physiological NF-kappaB inducer, interleukin-1beta (IL-1beta), and anti-apoptotic Bcl-2 family proteins on the 53BP2S-mediated apoptosis. We found that both NF-kappaB 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.
Takahashi
Naoko
N
Department of Molecular and Cellular Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Kobayashi
Shinya
S
Kajino
Shinichi
S
Imai
Kenichi
K
Tomoda
Keisuke
K
Shimizu
Shigeomi
S
Okamoto
Takashi
T
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001562:Benzimidazoles / Q000032:analysis; D002352:Carrier Proteins / Q000494:pharmacology*; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D004441:Ecdysterone / Q000031:analogs & derivatives / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009930:Organic Chemicals / Q000032:analysis; D010190:Pancreatic Neoplasms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; D001562:Benzimidazoles; D002352:Carrier Proteins; D016328:NF-kappa B; D009930:Organic Chemicals; D019253:Proto-Oncogene Proteins c-bcl-2; C090468:TP53BP2 protein, human; C485184:enhanced green fluorescent protein; C447680:hoechst 32258; C107472:red dye CMXRos; D049452:Green Fluorescent Proteins; D004441:Ecdysterone; C008999:ponasterone A; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases