The Polo-related kinase Cdc5 activates and is destroyed by the mitotic cyclin destruction machinery in S. cerevisiae

AbstractBackground: Following chromosome segregation in anaphase, ubiquitin-dependent degradation of mitotic cyclins contributes to the exit from mitosis. A key step in this process is catalyzed by a ubiquitin–protein ligase known as the anaphase-promoting complex (APC), the regulation of which is poorly understood. The Polo-related protein kinase Cdc5 in Saccharomyces cerevisiae might encode a regulator of the APC, because cdc5 mutant cells arrest with a late mitotic phenotype similar to that observed in cells with defective cyclin destruction.Results: We investigated the role of Cdc5 in the regulation of mitotic cyclin degradation. In cdc5-1 mutant cells, we observed a defect in the destruction of cyclins and a reduction in the cyclin–ubiquitin ligase activity of the APC. Overexpression of CDC5 resulted in increased APC activity and mitotic cyclin destruction in asynchronous cells or in cells arrested in metaphase. CDC5 mutation or overexpression did not affect the degradation of the APC substrate Pds 1, which is normally degraded at the metaphase-to-anaphase transition. Cyclin-specific APC activity in cells overexpressing CDC5 was reduced in the absence of the APC regulatory proteins Hct 1 and Cdc20. In G1, Cdc5 itself was degraded by an APC-dependent and Hct1-dependent mechanism.Conclusions: We conclude that Cdc5 is a positive regulator of cyclin-specific APC activity in late mitosis. Degradation of Cdc5 in G1 might provide a feedback mechanism by which the APC destroys its activator at the onset of the next cell cycle

The Role of Horseshoe Crabs in the Biomedical Industry and Recent Trends Impacting Species Sustainability

Every year the Atlantic horseshoe crab (Limulus polyphemus) arrives on shore to spawn, a sight once taken for granted. However, in addition to the gradual climate changes impacting all ecosystems, commercial demand from the widespread application of Atlantic horseshoe crab blood in industrial endotoxin testing and steady use as eel and whelk bait has brought the future of this enduring species into question. In response, regulations have been adopted to enhance the traceability and record keeping of horseshoe crab harvest, which has historically been difficult to track. However, these regulations do not restrict or limit LAL harvest in any significant manner. Still, sometimes-lethal biomedical bleeding process and associated behavioral changes pose a risk to horseshoe crab viability after bleeding and once returned to the waters. As a result, regulators and environmentalists are concerned that current trends and overfishing of this marine arthropod will significantly impact the surrounding ecosystem. This review examines their role and recent trends in the biomedical industry that are impacting these ancient creatures and the derivative effect on shorebirds, while considering emerging alternatives where feasible, as well as ways to ensure sustainable and pragmatic harvesting strategies. Ultimately, healthy populations of horseshoe crabs are vital to restoring and maintaining ecosystems while balancing the need for medical and research applications entirely dependent on these unique creatures