A new pathway to degrade cyclin B1
Heighington, Cassandra Sheila
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Cyclin B1 is the major regulator of M phase and it is widely conserved in eukaryotes. The anaphase-promoting factor, APC, targets cyclin B1 for degradation during the metaphase-to-anaphase transition. Inactivating another ubiquitin ligase, the CRL2ZYG-11 complex has many phenotypes; one of them is increased levels of cyclin B1. Here we used a forward genetic screen for zyg-11 suppressors and identified a mutation in CYB-2.1. Reducing the overall levels of cyclin B1/2.1/2.2 rescued the zyg-11 lethality, suggesting that the CRL2ZYG-11 complex reduces the level of cyclin B. We tested the interaction between ZYG-11 and CYB-1 to determine if the CRL2ZYG-11 is directly targeting CYB-1 for degradation, along with APC. We found that CRL2ZYG-11 directly binds and regulates CYB-1 in C. elegans meiosis and mitosis. To determine if this level of cyclin B regulation is conserved, we knocked down ZYG11A/B in human cells. We found an increased level of cyclin B1 during late metaphase when ZYG11A/B are knocked down. We also found that ZYG11B directly binds to cyclin B1, suggesting that the regulation of cyclin B by the CRL2ZYG11A/B complex is conserved in humans.