PMID:22621898

Citation	Hu, CK, Ozlü, N, Coughlin, M, Steen, JJ and Mitchison, TJ (2012) Plk1 negatively regulates PRC1 to prevent premature midzone formation before cytokinesis. Mol. Biol. Cell 23:2702-11
Abstract	To achieve mitosis and cytokinesis, microtubules must assemble into distinct structures at different stages of cell division-mitotic spindles to segregate the chromosomes before anaphase and midzones to keep sister genomes apart and guide the cleavage furrow after anaphase. This temporal regulation is believed to involve Cdk1 kinase, which is inactivated in a switch-like way after anaphase. We found that inhibiting Plk1 caused premature assembly of midzones in cells still in metaphase, breaking the temporal regulation of microtubules. The antiparallel microtubule-bundling protein PRC1 plays a key role in organizing the midzone complex. We found that Plk1 negatively regulates PRC1 through phosphorylation of a single site, Thr-602, near the C-terminus of PRC1. We also found that microtubules stimulated Thr-602 phosphorylation by Plk1. This creates a potential negative feedback loop controlling PRC1 activity. It also made the extent of Thr-602 phosphorylation during mitotic arrest dependent on the mechanism of the arresting drug. Unexpectedly, we could not detect a preanaphase regulatory role for Cdk1 sites on PRC1. We suggest that PRC1 is regulated by Plk1, rather than Cdk1 as previously proposed, because its activity must be spatiotemporally regulated both preanaphase and postanaphase, and Cdk1 activity is too binary for this purpose.
Links	PubMed PMC3395659 Online version:10.1091/mbc.E12-01-0058
Keywords	CDC2 Protein Kinase/metabolism; Cell Cycle Proteins/metabolism; Cell Line, Tumor; Cytokinesis/physiology; HeLa Cells; Humans; Microtubules/metabolism; Mitosis/physiology; Mitotic Spindle Apparatus/metabolism; Phosphorylation; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PLK1		GO:1901673: regulation of spindle assembly involved in mitosis	ECO:0000314:		P		Figure 1 - "Plk1 activity prevents premature midzone bundles forming in metaphase"	complete CACAO 7245
HUMAN:PLK1		GO:0001934: positive regulation of protein phosphorylation	ECO:0000315:		P		Figure 2 -" Plk1 phosphorylates PRC1"	complete CACAO 7246
HUMAN:PLK1	involved_in	GO:1901673: regulation of mitotic spindle assembly	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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