Journal article
Dual regulation of the anaphase promoting complex in human cells by cyclin A-Cdk2 and cyclin A-Cdk1 complexes
Cell cycle (Georgetown, Tex.), v 5(6), pp 661-666
Mar 2006
PMID: 16582612
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
In mammalian somatic cells, the Anaphase Promoting Complex (APC) is inactivated during S phase by active cyclin A-Cyclin dependent kinase (Cdk) 2 complexes promoting accumulation of mitotic regulators, such as cyclin B and Polo like kinase 1 (Plk1). However, mitotic entry does not appear to be perturbed in some human cancer cells or in normal mouse cells following Cdk2 RNA interference (i) or deletion of the Cdk2 gene. These results suggest functional complementation of APC regulation by a compensatory kinase. Using Plk1 protein level as readout of APC activity, we show that APC is inactivated during S phase in human cells by both cyclin A-Cdk2 and cyclin A-Cdk1 complexes. Expression of a dominant negative mutant of Cdk2 or Cdk2 RNAi in early S phase destabilizes Plk1 as it begins to accumulate. However, this effect wanes in late S phase, where destabilization of Plk1 also requires Cdk1 RNAi. Although Cdk2 is the dominant partner of cyclin A in these settings, cyclin A also binds Cdk1. Both complexes bind the APC targeting factor Cdh1, but Cdk1 complexes are inactive in early S phase, accounting for the stronger regulation of APC function by Cdk2. These results provide further evidence that cyclin A-Cdk2 and -Cdk1 complexes display overlapping and partially redundant roles in preparing cells for mitosis, through regulation of the APC.
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Details
- Title
- Dual regulation of the anaphase promoting complex in human cells by cyclin A-Cdk2 and cyclin A-Cdk1 complexes
- Creators
- Jayashree Mitra - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA. Jayashree.Mitra@drexel.eduGreg H EndersJane Azizkhan-CliffordKathleen L Lengel
- Publication Details
- Cell cycle (Georgetown, Tex.), v 5(6), pp 661-666
- Publisher
- United States
- Grant note
- R01 GM065514-01 / NIGMS NIH HHS R01 CA91681 / NCI NIH HHS K01 DK61280-04 / NIDDK NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000238282400025
- Scopus ID
- 2-s2.0-33645298454
- Other Identifier
- 991014878065704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology