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NF-κB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2

Abstract

Nuclear factor κB (NF-κB) is a transcription factor that controls the expression of many cellular and viral genes. The p65 (RelA) subunit plays a critical role as a transcriptional activator and recent observations have highlighted its role in the control of apoptosis. Here we report that 53BP2, a protein previously identified by interaction with wild type p53 and Bcl-2, also binds to p65 in a yeast two-hybrid system. This specific interaction was confirmed by pull-down assay in vitro and by a mammalian two-hybrid assay in vivo. We observed that full-length 53BP2 fused to GFP had a punctate distribution in cytoplasm, predominantly in perinuclear region whereas the N-terminal 53BP2 localized in cytoplasm and C-terminal 53BP2 localized in the nucleus. Furthermore, we found that overexpression of GFP-53BP2 induced apoptosis in transiently transfected cells. Neither the N-terminal nor the C-terminal of 53BP2 fused to GFP induced cell death. Interestingly, co-transfection with a p65 expression plasmid significantly inhibited 53BP2-induced cell death. The previous findings that 53BP2 bound to p53 and Bcl-2 together with our present observations suggest that 53BP2 may play a central role in the regulation of apoptosis and cell growth.

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Acknowledgements

We thank S Inuzuka, M Suganuma and T Tetsuka for helpful suggestions. This work was supported by grants-in-aid from the Ministry of Health and Welfare, the Ministry of Education, Science and Culture of Japan and from the Human Science Foundation. J-P Yang is a research fellow of the Japan Society for the Promotion of Science.

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Yang, JP., Hori, M., Takahashi, N. et al. NF-κB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene 18, 5177–5186 (1999). https://doi.org/10.1038/sj.onc.1202904

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