Year: 2022
Type: article
Abstract: 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. We employed live imaging to observe HeLa cells with fluorescently tagged histones treated with MKLP2i and discovered a pronounced chromosome congression defect. We show that MKLP2 facilitates error correction, as inhibited cells have a significant increase in unstable, syntelic kinetochore-microtubule attachments. We find that the aberrant attachments are accompanied by elevated Aurora kinase (A and B) activity and phosphorylation of the downstream target HEC1 (also known as NDC80) at Ser55. Finally, we show that MKLP2 inhibition results in aneuploidy, confirming that MKLP2 safeguards cells against chromosomal instability. This article has an associated First Person interview with the first author of the paper.
Source: Journal of Cell Science
DOI: 10.1242/jcs.259560
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
Awards: G1133437983, Defining the molecular mechanisms regulating the hexosamine-N-glycosylation pathway in glioblastoma, The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve Health, G1858189645, G216896791, G364506074, Dissecting functional interplay of deubiquitinases and the cell cycle machinery, Ohio State University Neuroscience Center Core, G9000020092, G9000266250, Cancer Center Support Grant, Massey Cancer Center - Cancer Center Support Grant, Evolution of gliomas during treatment and resistance, Determining the role of lipid droplets and their therapeutic potential in glioblastoma, G900945448, Mechanisms of Spindle Assembly Checkpoint Silencing
OpenAlex ID: W4281892178