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Centralspindlin assembly and 2 phosphorylations on MgcRacGAP by Polo-like kinase 1 initiate Ect2 binding in early cytokinesis
Journal article   Open access   Peer reviewed

Centralspindlin assembly and 2 phosphorylations on MgcRacGAP by Polo-like kinase 1 initiate Ect2 binding in early cytokinesis

Hyunjung Kim, Feng Guo, Sarang Brahma, Yongna Xing and Mark E Burkard
Cell cycle (Georgetown, Tex.), Vol.13(18), pp.2952-2961
09/17/2014
DOI: 10.4161/15384101.2014.947201
PMCID: PMC4614826
PMID: 25486482
url
https://doi.org/10.4161/15384101.2014.947201View
Published (Version of record) Open Access

Abstract

Cytokinesis is the final step of cell division which partitions genetic and cytosolic content into daughter cells. Failed cytokinesis causes polyploidy, genetic instability, and cancer. Kinases use phosphorylation to regulate the timing and location of the cytokinetic furrow. Polo-like kinase 1 (Plk1) is an essential mitotic kinase that triggers cytokinesis by phosphorylating MgcRacGAP to create a docking site for Ect2 at the central spindle. Ect2 binds to MgcRacGAP via its N-terminal BRCT domain (BRCA1 C-terminal), which docks at specific phosphorylated residues. Here we investigate the minimal Plk1-dependent phosphorylation sites required for cytokinesis onset. We demonstrate that phosphorylation of the major MgcRacGAP site, S157, is necessary but not sufficient to bind the Ect2 BRCT domain. Phosphorylation of an additional residue on MgcRacGAP at S164 is also required to elicit efficient binding. Surprisingly, BRCT binding additionally requires MKLP1 and its cognate interacting N-terminal domain of MgcRacGAP. Our findings indicate that central spindle assembly and 2 Plk1-dependent phosphorylations are required to establish efficient binding of the Ect2 BRCT in early cytokinesis. We propose that these requirements establish a high threshold to restrain premature or ectopic cytokinesis.
 Cyk4 Ect2 MKLP1 Plk1 RACGAP1

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