To cell cycle, swing the APC/C.
For successful mitosis, Cyclin B1 and Securin must be degraded efficiently before anaphase. Destruction of these mitotic regulators by the 26S proteasome is the result of their poly-ubiquitination by a multi-subunit E3 ligase: the Anaphase-Promoting Complex or Cyclosome (APC/C). Clearly, the APC/C is not just important for mitosis. Destruction of APC/C substrates such as Cdc20, Plk1, Aurora A and Skp2 directs events in G1. Strikingly, the APC/C needs to stay active even in quiescent cells to keep them out of the cell cycle and forms an intriguing link with pRb. An inactive APC/C stabilizes Geminin, Cyclin A and Cyclin B1, thereby securing completion of DNA synthesis and progression through G2-phase. In prometaphase the APC/C becomes active again, but is controlled by the spindle assembly checkpoint. Here we discuss how the APC/C is either held in check or released. We argue that shedding more light on the APC/C is also important to understand cancer and could help the design of treatment.
Department of Medical Oncology, University Medical Center, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Renske
R
van Leuken
Linda
L
Clijsters
Rob
R
Wolthuis
D064173:Anaphase-Promoting Complex-Cyclosome; D015703:Antigens, CD; D016203:CDC2 Protein Kinase / Q000502:physiology; D015820:Cadherins / Q000502:physiology; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D019926:Cyclin B / Q000378:metabolism*; D004249:DNA Damage; D016195:G2 Phase / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000209:etiology; D016196:S Phase / Q000502:physiology; D064249:Securin; D008941:Spindle Apparatus / Q000187:drug effects / Q000502:physiology; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D054875:Ubiquitination
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D019926:Cyclin B; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D016203:CDC2 Protein Kinase