Nature Cell Biology
6, 849 - 860 (2004)
Published online: 8 August 2004; | doi:10.1038/ncb1159
Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection functionYanyan Hao1, 2, Keiko Sekine1, Atsushi Kawabata1, Hitoshi Nakamura1, 3, Toshiyasu Ishioka1, Hirokazu Ohata1, Ryohei Katayama1, Chizuko Hashimoto1, Xiaodong Zhang1, 4, Tetsuo Noda5, Takashi Tsuruo1, 6
& Mikihiko Naito1, 21
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. 2
These authors contributed equally to this work. 3
Present address: Takeda Chemical Industries Ltd., 2-17-85 Jyuso-Honmachi, Yodogawa-ku, Osaka 532-8686, Japan. 4
Present address: Institute for Molecular Biology, College of Life Sciences, Nankai University, 94, Weijing Road, Tianjin, 300071, China. 5
Cancer Institute, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan. 6
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1, Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Correspondence should be addressed to Mikihiko Naito mnaito@iam.u-tokyo.ac.jpApollon (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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