P120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis

Robert A.H. Van De Ven, Jolien S. De Groot, Danielle Park, Robert Van Domselaar, Danielle De Jong, Karoly Szuhai, Elsken Van Der Wall, Oscar M. Rueda, H. Raza Ali, Carlos Caldas, Paul J. Van Diest, Martin W. Hetzer, Erik Sahai, Patrick W.B. Derksen

Research output: Contribution to journalArticle

Abstract

Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell-cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell-cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer.

Original languageEnglish (US)
Article number13874
JournalNature communications
Volume7
DOIs
StatePublished - Dec 22 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'P120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis'. Together they form a unique fingerprint.

  • Cite this

    Van De Ven, R. A. H., De Groot, J. S., Park, D., Van Domselaar, R., De Jong, D., Szuhai, K., Van Der Wall, E., Rueda, O. M., Ali, H. R., Caldas, C., Van Diest, P. J., Hetzer, M. W., Sahai, E., & Derksen, P. W. B. (2016). P120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis. Nature communications, 7, [13874]. https://doi.org/10.1038/ncomms13874