Abstract
Apollon (also known as BRUCE or BIRC6) is a large protein containing baculoviral-IAP-repeat (BIR) and ubiquitin-conjugating enzyme (UBC) domains at the amino- and carboxy termini, respectively. Apollon inhibits apoptosis, but its molecular and physiological function remains unclear. Here we report that Apollon binds to, ubiquitinates and facilitates proteasomal degradation of SMAC and caspase-9, which both contain IAP-binding motifs. Targeted disruption of Apollon in mice caused embryonic and neonatal lethality. Notably, SMAC induced apoptosis in Apollon-deficient cells, but not in Apollon-expressing cells. Furthermore, the IAP-binding motif of SMAC was required to induce apoptosis in Apollon-deficient cells. These results suggest that Apollon has an essential function in preventing SMAC-induced apoptosis.
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Acknowledgements
We thank R. Takahashi for critical reading of the manuscript, A. Tomida and N. Fujita for helpful discussion and H. Yamanaka and S. Ito for assistance in generation of the Bruce-knockout mice. This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, Sports and Culture, Japan.
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Hao, Y., Sekine, K., Kawabata, A. et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nat Cell Biol 6, 849–860 (2004). https://doi.org/10.1038/ncb1159
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DOI: https://doi.org/10.1038/ncb1159
