Mitotic regulation of the anaphase-promoting complex |
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Authors: | D J Baker M M Dawlaty P Galardy J M van Deursen |
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Institution: | (1) Departments of Pediatric and Adolescent Medicine, Biochemistry and Molecular Biology, Mayo Clinic, 200 1st ST SW, Guggenheim 1507, Rochester, Minnesota 55905, USA |
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Abstract: | Orderly progression through mitosis is regulated by the anaphase-promoting complex/cyclosome (APC/C), a large multiprotein
E3 ubiquitin ligase that targets key mitotic regulators for destruction by the proteasome. APC/C has two activating subunits,
Cdc20 and Cdh1. The well-established view is that Cdc20 activates APC/C from the onset of mitosis through the metaphase-anaphase
transition, and that Cdh1 does so from anaphase through G1. Recent work, however, indicates that Cdh1 also activates APC/C
in early mitosis and that this APC/C pool targets the anaphase inhibitor securin. To prevent premature degradation of securin,
the nuclear transport factors Nup98 and Rae1 associate with APC/CCdh1-securin complexes. In late metaphase, when all kinetochores are attached to spindle microtubules and the spindle assembly
checkpoint is satisfied, Nup98 and Rae1 are released from these complexes, thereby allowing for prompt ubiquitination of securin
by APC/CCdh1. This, and other mechanisms by which the catalytic activity of APC/C is tightly regulated to ensure proper timing of degradation
of each of its mitotic substrates, are highlighted.
Received 8 October 2006; received after revision 24 November 2006; accepted 8 January 2007 |
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Keywords: | Anaphase-promoting complex APC/C spindle assembly checkpoint Cdc20 Cdh1 |
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