title: APOLLON protein promotes early mitotic CYCLIN A degradation independent of the spindle assembly checkpoint.
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.
authors.affiliation: From the Institute of Molecular and Cellular Biosciences.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohata
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Ohoka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawabata
authors.forename: Mikihiko
authors.initials: M
authors.lastname: Naito
mesh_terms: D059447:Cell Cycle Checkpoints / Q000502:physiology*; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D020298:U937 Cells
chemical_list: C401541:BIRC6 protein, human; D019925:Cyclin A; D019926:Cyclin B; D051034:Inhibitor of Apoptosis Proteins
keywords: APC/C; APPOLON; Cell Cycle; Cyclin A; Cyclins; Mitosis; Protein Degradation; Spindle Assembly Checkpoint; Ubiquitin