Chromokinesin KIF4A teams up with stathmin 1 to regulate abscission in a SUMO-dependent manner

ABSTRACT Cell division ends when two daughter cells physically separate via abscission, the cleavage of the intercellular bridge. It is not clear how the anti-parallel microtubule bundles bridging daughter cells are severed. Here, we present a novel abscission mechanism. We identified chromokinesin KIF4A, which is adjacent to the midbody during cytokinesis, as being required for efficient abscission. KIF4A is regulated by post-translational modifications. We evaluated modification of KIF4A by the ubiquitin-like protein SUMO. We mapped lysine 460 in KIF4A as the SUMO acceptor site and employed CRISPR-Cas9-mediated genome editing to block SUMO conjugation of endogenous KIF4A. Failure to SUMOylate this site in KIF4A delayed cytokinesis. SUMOylation of KIF4A enhanced the affinity for the microtubule destabilizer stathmin 1 (STMN1). We here present a new level of abscission regulation through the dynamic interactions between KIF4A and STMN1 as controlled by SUMO modification of KIF4A. Summary: A new mechanism of abscission regulation is identified through the dynamic interactions between KIF4A and stathmin 1 as controlled by SUMO modification of KIF4A.

• Publication year

  2020

• Venue

  Journal of Cell Science

• Publication date

  2020-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1242/jcs.248591PMID 32591481PMCID 7390632
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• [Genome engineering using the CRISPR-Cas9 system and applications in cancer research].

  2018cited by this paper
• A SUMO-Dependent Protein Network Regulates Chromosome Congression during Oocyte Meiosis

  2017cited by this paper
• SUMO and the robustness of cancer

  2017cited by this paper
• SUMOylation of human septins is critical for septin filament bundling and cytokinesis

  2017cited by this paper
• SUMO conjugation – a mechanistic view

  2017cited by this paper
• Cooperativity of the SUMO and Ubiquitin Pathways in Genome Stability

  2016cited by this paper
• A high-yield double-purification proteomics strategy for the identification of SUMO sites

  2016cited by this paper
• Direct evidence for the interaction of stathmin along the length and the plus end of microtubules in cells

  2016cited by this paper
• A comprehensive compilation of SUMO proteomics

  2016cited by this paper
• Genome engineering using CRISPR-Cas9 system.

  2015cited by this paper
• Characterization of the Loss of SUMO Pathway Function on Cancer Cells and Tumor Proliferation

  2015cited by this paper
• SUMOylation-Mediated Regulation of Cell Cycle Progression and Cancer.

  2015cited by this paper
• Identification of SUMO‐2/3‐modified proteins associated with mitotic chromosomes

  2015cited by this paper
• 2016 update of the PRIDE database and its related tools

  2015influential reference
• Septins promote F-actin ring formation by crosslinking actin filaments into curved bundles

  2014cited by this paper
• Uncovering Global SUMOylation Signaling Networks in a Site-Specific Manner

  2014influential reference
• Cytokinetic abscission: molecular mechanisms and temporal control.

  2014cited by this paper
• Uncovering SUMOylation dynamics during cell-cycle progression reveals FoxM1 as a key mitotic SUMO target protein.

  2014cited by this paper
• Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4A

  2013cited by this paper
• Ubiquitin ligases and cell cycle control.

  2013cited by this paper
• Sumoylation: a regulatory protein modification in health and disease.

  2013cited by this paper
• Genome engineering using the CRISPR-Cas9 system

  2013cited by this paper
• Polo-like kinases.

  2013cited by this paper
• Histone phosphorylation

  2012cited by this paper
• Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair.

  2012cited by this paper
• KIF4 regulates midzone length during cytokinesis.

  2011cited by this paper
• The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly

  2011cited by this paper
• Cortical Constriction During Abscission Involves Helices of ESCRT-III–Dependent Filaments

  2011cited by this paper
• Determinants of myosin II cortical localization during cytokinesis.

  2010cited by this paper
• Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.

  2010influential reference
• Post-translational modifications in signal integration

  2010cited by this paper
• The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition

  2010cited by this paper
• Orchestrating nuclear envelope disassembly and reassembly during mitosis

  2009cited by this paper
• Emerging roles of the SUMO pathway in mitosis

  2008cited by this paper
• Spastin Couples Microtubule Severing to Membrane Traffic in Completion of Cytokinesis and Secretion

  2008cited by this paper
• Final stages of cytokinesis and midbody ring formation are controlled by BRUCE.

  2008cited by this paper
• Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B

  2008cited by this paper
• Interactions between myosin and actin crosslinkers control cytokinesis contractility dynamics and mechanics.

  2008cited by this paper
• Distinct pathways for the early recruitment of myosin II and actin to the cytokinetic furrow.

  2008cited by this paper
• SUMO-2/3 modification and binding regulate the association of CENP-E with kinetochores and progression through mitosis.

  2008cited by this paper
• Mammalian SEPT2 is required for scaffolding nonmuscle myosin II and its kinases.

  2007cited by this paper
• Spatiotemporal control of spindle midzone formation by PRC1 in human cells.

  2006cited by this paper
• The SUMO pathway is essential for nuclear integrity and chromosome segregation in mice.

  2005cited by this paper
• Stabilization of PML nuclear localization by conjugation and oligomerization of SUMO-3

  2005cited by this paper
• SUMO modification of the ubiquitin-conjugating enzyme E2-25K

  2005cited by this paper
• Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis.

  2005cited by this paper
• Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation

  2004cited by this paper
• Polo-like kinases and the orchestration of cell division

  2004cited by this paper
• Kinesin superfamily protein member 4 (KIF4) is localized to midzone and midbody in dividing cells

  2004cited by this paper
• Identification of a SUMO-binding motif that recognizes SUMO-modified proteins.

  2004cited by this paper
• Ubc9 is essential for viability of higher eukaryotic cells.

  2002cited by this paper
• Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1.

  2002cited by this paper
• The anaphase-promoting complex: proteolysis in mitosis and beyond.

  2002cited by this paper
• A new protease required for cell-cycle progression in yeast

  1999cited by this paper
• Control of microtubule dynamics by oncoprotein 18: dissection of the regulatory role of multisite phosphorylation during mitosis

  1997influential reference
• How Proteolysis Drives the Cell Cycle

  1996cited by this paper
• Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex

  1995cited by this paper
• Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins

  1995cited by this paper
• Cleavage furrow: timing of emergence of contractile ring actin filaments and establishment of the contractile ring by filament bundling in sea urchin eggs.

  1994cited by this paper
• Mitosis in transition.

  1994cited by this paper
• Occurrence of fibers and their association with talin in the cleavage furrows of PtK2 cells.

  1994cited by this paper
• Cyclin is degraded by the ubiquitin pathway

  1991cited by this paper
• Analysis of mutation in human cells by using an Epstein-Barr virus shuttle system

  1987cited by this paper
• Post-Translational Modifications

  1982cited by this paper
• Filamin concentration in cleavage furrow and midbody region: frequency of occurrence compared with that of alpha-actinin and myosin

  1980cited by this paper
• Terminal phase of cytokinesis in D-98S cells

  1977cited by this paper
• Histone phosphorylation in late interphase and mitosis.

  1973cited by this paper
• Cytokinesis: filaments in the cleavage furrow.

  1968cited by this paper

• KIF4A in disease pathogenesis and therapeutics: from molecular mechanisms to clinical translation

  2025cites this paper
• KIF4A promotes epithelial–mesenchymal transition by activating the TGF-β/SMAD signaling pathway in glioma cells

  2024cites this paper
• X‐Linked Bilateral Polymicrogyria With Epilepsy and Intellectual Disability Associated With a Novel KIF4A Variant

  2024cites this paper
• Regulation of the mitotic chromosome folding machines

  2022cites this paper
• A Novel Five-Gene Signature Related to Clinical Outcome and Immune Microenvironment in Breast Cancer

  2022cites this paper
• Signalling mechanisms and cellular functions of SUMO

  2022cites this paper
• Microarray screening reveals two non-conventional SUMO-binding modules linked to DNA repair by non-homologous end-joining

  2021cites this paper