APOLLON Protein Promotes Early Mitotic CYCLIN A Degradation Independent of the Spindle Assembly Checkpoint |
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Authors: | Ryo Kikuchi Hirokazu Ohata Nobumichi Ohoka Atsushi Kawabata Mikihiko Naito |
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Affiliation: | From the ‡Institute of Molecular and Cellular Biosciences.;§Graduate School of Pharmaceutical Sciences, and ;¶Graduate School of Frontier Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032 and ;the ‖National Institute of Health Sciences, Setagaya-ku, Tokyo 158-8501, Japan |
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Abstract: | In the mammalian cell cycle, both CYCLIN A and CYCLIN B are required for entry into mitosis, and their elimination is also essential to complete the process. During mitosis, CYCLIN A and CYCLIN B are ubiquitylated by the anaphase-promoting complex/cyclosome (APC/C) and then subjected to proteasomal degradation. However, CYCLIN A, but not CYCLIN B, begins to be degraded in the prometaphase when APC/C is inactivated by the spindle assembly checkpoint (SAC). Here, we show that APOLLON (also known as BRUCE or BIRC6) plays a role in SAC-independent degradation of CYCLIN A in early mitosis. APPOLON interacts with CYCLIN A that is not associated with cyclin-dependent kinases. APPOLON also interacts with APC/C, and it facilitates CYCLIN A ubiquitylation. In APPOLON-deficient cells, mitotic degradation of CYCLIN A is delayed, and the total, but not the cyclin-dependent kinase-bound, CYCLIN A level was increased. We propose APPOLON to be a novel regulator of mitotic CYCLIN A degradation independent of SAC. |
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Keywords: | Cell Cycle Cyclins Mitosis Protein Degradation Ubiquitin APC/C APPOLON Cyclin A Spindle Assembly Checkpoint |
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