Mitotic kinesin-like protein 2 (MKLP2; also known as KIF20A) is a motor protein with a well-established function in promoting cytokinesis. However, our results with siRNAs targeting MKLP2 and small-molecule inhibitors of MKLP2 (MKLP2i) suggest that it also has a function earlier in mitosis, prior to anaphase. In this study, we provide direct evidence that MKLP2 facilitates chromosome congression in prometaphase.
View Article and Find Full Text PDFThe deubiquitinating enzyme USP37 is known to contribute to timely onset of S phase and progression of mitosis. However, it is not clear if USP37 is required beyond S-phase entry despite expression and activity of USP37 peaking within S phase. We have utilized flow cytometry and microscopy to analyze populations of replicating cells labeled with thymidine analogs and monitored mitotic entry in synchronized cells to determine that USP37-depleted cells exhibited altered S-phase kinetics.
View Article and Find Full Text PDFAPC/C is a ubiquitin ligase with roles in numerous diverse processes, including control of cellular proliferation and multiple aspects of the DNA damage response. Precise regulation of APC/C activity is central to efficient cell-cycle progression and cellular homeostasis. Here, we have identified Cdh1 as a direct substrate of the replication stress checkpoint effector kinase Chk1 and demonstrate that Chk1-mediated phosphorylation of Cdh1 contributes to its recognition by the SCF ubiquitin ligase, promotes efficient S-phase entry, and is important for cellular proliferation during otherwise unperturbed cell cycles.
View Article and Find Full Text PDFThe purpose of this study was to develop a pain assessment tool utilized by certified nursing assistant (CNA) direct-care providers for nursing home residents with dementia and to examine the impact of such a tool on their function, behavior, or medication use. In the first phase, 41 items from an observational pain assessment tool were correlated with an objective pain "gold standard"; 12 statistically significant items were retained and used in the CNA pain assessment tool. Symmetry analysis was then conducted to determine if this resulted in any significant change in resident function, behavior, or medication use.
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