High mitotic activity of Polo-like kinase 1 is required for chromosome segregation and genomic integrity in human epithelial cells.

ABSTRACT: Protein kinases play key roles in regulating human cell biology, but manifold substrates and functions make it difficult to understand mechanism. We tested whether we could dissect functions of a pleiotropic mitotic kinase, Polo-like kinase 1 (Plk1), via distinct thresholds of kinase activity. We accomplished this by titrating Plk1 activity in RPE1 human epithelial cells using chemical genetics and verifying results in additional lines. We found that distinct activity thresholds are required for known functions of Plk1 including (from low to high activity) bipolar spindle formation, timely mitotic entry, and formation of a cytokinesis cleavage furrow. Subtle losses in Plk1 activity impaired chromosome congression and produced severe anaphase dysfunction characterized by poor separation of

SUBMITTER: Lera RF 

PROVIDER: S-EPMC3525009 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature