Abstract
p73 is a nuclear protein that is similar in structure and function to p53. Notably, the C-terminal region of p73 has a regulatory function, through interactions with a positive or negative regulator. In this study, we use the yeast two-hybrid technique to identify a novel p73β binding protein, designated amphiphysin IIb-1. Amphiphysin IIb-1 is one of the splicing variants of amphiphysin II, and has a shorter protein product than amphiphysin IIb, which has been previously reported. We confirmed that amphiphysin IIb-1 binds full-length p73β, both in vitro and in vivo. This association is mediated via the SH3 domain of amphiphysin IIb-1 and C-terminal amino acids 321–376 of p73β. Double immunofluorescence patterns revealed that p73β is relocalized to the cytoplasm in the presence of amphiphysin IIb-1. Overexpression of amphiphysin IIb-1 was found to significantly inhibit the transcriptional activity of p73β in a dose-dependent manner. In addition, the cell death function of p73β was inhibited by amphiphysin IIb-1. These findings offer a new insight into the regulation mechanism of p73β, and suggest that amphiphysin IIb-1 modulates p73β function by direct binding.
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Acknowledgements
We gratefully thank Dr JY Lee of Hallym University for the p21-Luc plasmid. We also thank Dr HS Lim of the Catholic Medical Center for helpful comments on the yeast two-hybrid technique. This work was supported by grant from the Korea Ministry of Health and Welfare (HMP-99-B-02-002) and the Research Grant of Chung-Ang University.
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Kim, KC., Kim, TS., Kang, KH. et al. Amphiphysin IIb-1, a novel splicing variant of amphiphysin II, regulates p73β function through protein-protein interactions. Oncogene 20, 6689–6699 (2001). https://doi.org/10.1038/sj.onc.1204839
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DOI: https://doi.org/10.1038/sj.onc.1204839
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