The APC/C recruits cyclin B1-Cdk1-Cks in prometaphase before D box recognition to control mitotic exit.
Summary of "The APC/C recruits cyclin B1-Cdk1-Cks in prometaphase before D box recognition to control mitotic exit."
The ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated at prometaphase by mitotic phosphorylation and binding of its activator, Cdc20. This initiates cyclin A degradation, whereas cyclin B1 is stabilized by the spindle checkpoint. Upon checkpoint release, the RXXL destruction box (D box) was proposed to direct cyclin B1 to core APC/C or Cdc20. In this study, we report that endogenous cyclin B1-Cdk1 is recruited to checkpoint-inhibited, phosphorylated APC/C in prometaphase independently of Cdc20 or the cyclin B1 D box. Like cyclin A, cyclin B1 binds the APC/C by the Cdk cofactor Cks and the APC3 subunit. Prior binding to APC/C(Cdc20) makes cyclin B1 a better APC/C substrate in metaphase, driving mitotic exit and cytokinesis. We conclude that in prometaphase, the phosphorylated APC/C can recruit both cyclin A and cyclin B1 in a Cks-dependent manner. This suggests that the spindle checkpoint blocks D box recognition of APC/C-bound cyclin B1, whereas distinctive complexes between the N terminus of cyclin A and Cdc20 evade checkpoint control.
Affiliation
Division of Molecular Biology and 2 Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
Journal Details
This article was published in the following journal.
Name: The Journal of cell biology
ISSN: 1540-8140
Pages: 587-602
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20733055
- DOI: http://dx.doi.org/10.1083/jcb.200912084
Medical and Biotech [MESH] Definitions
Cyclin I
A cyclin subtype that is found abundantly in post-mitotic tissues. In contrast to the classical cyclins, its level does not fluctuate during the cell cycle.
Metaphase
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the MITOTIC SPINDLE APPARATUS prior to separation.
Prometaphase
The phase of cell nucleus division following PROPHASE, when the breakdown of the NUCLEAR ENVELOPE occurs and the MITOTIC SPINDLE APPARATUS enters the nuclear region and attaches to the KINETOCHORES.
Cyclin D
A cyclin subtype that is specific for CYCLIN-DEPENDENT KINASE 4 and CYCLIN-DEPENDENT KINASE 6. Unlike most cyclins, cyclin D expression is not cyclical, but rather it is expressed in response to proliferative signals. Cyclin D may therefore play a role in cellular responses to mitogenic signals.
Cyclin-dependent Kinase Inhibitor P27
A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.
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