KIF20B

KIF20B is a Kinesin-6 family motor that drives cytokinesis and neuronal morphogenesis through plus-end-directed transport on microtubules (PMID:11470801, PMID:31260385). Its N-terminal motor domain has intrinsic, microtubule-stimulated ATPase activity dependent on the conserved Lys-168, and the protein binds and bundles microtubules while acting as a slow plus-end-directed motor (PMID:11470801, PMID:31260385). During cytokinesis KIF20B localizes to central spindle microtubules and the midbody at sites distinct from KIF23/MKLP1 and KIF20A/MKLP2, where it is dispensable for midbody assembly but required to promote efficient furrow ingression and to coordinate late midbody maturation—anillin dispersal, ESCRT-III recruitment, and microtubule constriction-site formation (PMID:29167382); it cooperates with PRC1 at the midbody, and loss of either causes multinucleation and death (PMID:17409436). KIF20B protein abundance is controlled by a USP7→FBXO38→KIF20B stabilization cascade in which the deubiquitylase USP7 protects FBXO38, which in turn stabilizes KIF20B and maintains its midbody pool (PMID:30804394). In neural development KIF20B binds Shootin1 through a 57-residue tail domain and transports this cargo to the axonal growth cone, promoting PIP3 accumulation and the multipolar-to-bipolar transition during cortical neuron migration and axon morphogenesis (PMID:23864681, PMID:28359322). Loss of Kif20b disrupts midbody organization and abscission in cortical neural stem cells, leading to apoptosis and microcephaly (PMID:24173802).

1. 2001 High

   Established KIF20B as a bona fide motor enzyme by demonstrating intrinsic ATPase activity in its motor domain and linking its mitotic behavior to phosphoregulation and Pin1.

   Evidence In vitro ATPase assay with K168R active-site mutant, co-IP and pull-down with Pin1, in vivo phospho-labeling and cell-cycle analysis

   PMID:11470801

   Open questions at the time

   • No microtubule-dependent motility or directionality assessed
   • Functional consequence of Pin1 binding and Thr-1604 phosphorylation on motor activity unresolved
2. 2007 Medium

   Placed KIF20B in the cytokinesis machinery by showing it complexes with PRC1 at the midbody and is required to complete cell division.

   Evidence Reciprocal co-IP, midbody colocalization, and siRNA knockdown causing multinucleation/death in bladder cancer cells

   PMID:17409436

   Open questions at the time

   • Direct vs. indirect nature of the PRC1 interaction not resolved
   • Single cell-type context
3. 2013 High

   Defined a distinct neurodevelopmental role by identifying Shootin1 as a direct KIF20B cargo whose transport drives neuronal polarization.

   Evidence SPR Kd determination, co-IP from developing brain, FRAP-based cargo mobilization, shRNA, dominant-negative MBD, in vivo migration and epistasis

   PMID:23864681

   Open questions at the time

   • Whether motor ATPase activity drives Shootin1 transport not directly tested
   • Mechanism of PIP3 accumulation downstream of Shootin1 delivery unclear
4. 2013 High

   Connected KIF20B cytokinesis function to organismal phenotype, showing abscission failure in neural stem cells causes apoptosis and microcephaly rather than binucleation.

   Evidence magoo loss-of-function mouse mutant with midbody imaging, cortical cell counting, apoptosis assays

   PMID:24173802

   Open questions at the time

   • Molecular step of abscission requiring KIF20B not pinpointed in this study
   • Link between midbody mispositioning and apoptosis mechanistically undefined
5. 2014 Medium

   Linked KIF20B loss to p53/STAT3 signaling outcomes, framing its depletion as a route to mitotic arrest and postmitotic apoptosis in cancer.

   Evidence shRNA knockdown in hepatocellular carcinoma cells, Western blot for p53/phospho-STAT3, flow cytometry, xenograft

   PMID:25269478

   Open questions at the time

   • Whether p53/STAT3 effects are direct or secondary to cytokinesis failure unclear
   • No mechanistic connection between KIF20B motor activity and STAT3 phosphorylation
6. 2017 High

   Resolved the precise cytokinetic step KIF20B serves, distinguishing it from other Kinesin-6 motors and assigning it to late midbody maturation.

   Evidence siRNA in human cells with quantitative live imaging of furrow ingression and immunostaining for anillin and ESCRT-III

   PMID:29167382

   Open questions at the time

   • How KIF20B coordinates anillin dispersal and ESCRT-III recruitment mechanistically unknown
   • Direct binding partners at the constriction site not identified
7. 2017 Medium

   Extended the Shootin1-transport model to neurite morphogenesis, showing KIF20B-dependent growth-cone Shootin1 localization shapes axon caliber and branching.

   Evidence Kif20b mouse mutant cortical neurons with in vivo/in vitro imaging, live axon-extension imaging, Shootin1 immunostaining

   PMID:28359322

   Open questions at the time

   • Cause of abnormal microtubule organization in mutant axons not defined
   • Whether axon defects are cell-autonomous transport defects vs. cytokinesis history unclear
8. 2019 High

   Identified an upstream stability pathway controlling KIF20B abundance, defining the epistatic order USP7→FBXO38→KIF20B for midbody function.

   Evidence AP-MS, BioID, co-IP, siRNA, Western blot, midbody immunofluorescence, and rescue experiments

   PMID:30804394

   Open questions at the time

   • Mechanism by which FBXO38 stabilizes KIF20B independent of SCF unresolved
   • Whether stabilization is regulated dynamically across the cell cycle unknown
9. 2019 Medium

   Confirmed KIF20B as a microtubule-binding, microtubule-bundling, slow plus-end-directed motor and described its cell-cycle-dependent redistribution.

   Evidence In vitro microtubule-binding/bundling and ATPase assays plus monoclonal-antibody immunofluorescence in HEp2 cells and tissue

   PMID:31260385

   Open questions at the time

   • Single-antibody localization with limited mechanistic follow-up
   • Functional role of interphase nuclear localization undefined
10. 2018 Low

    Implicated KIF20B in cancer cell invasion via pseudopod/invadopodia localization and Gli1-mediated EMT.

    Evidence Immunofluorescence, siRNA/overexpression in colorectal cancer lines, migration/invasion assays, actin dynamics analysis

    PMID:29573464

    Open questions at the time

    • Low-confidence single-lab study with limited mechanistic depth
    • Connection between motor activity, actin dynamics, and Gli1 not established
    • Direct partners in invadopodia unidentified

• How KIF20B mechanically couples its plus-end-directed motor activity to specific late-abscission events (anillin dispersal, ESCRT-III recruitment, constriction-site formation) and whether the same motor activity powers Shootin1 cargo transport remain open.
• No structural model linking motor cycle to midbody maturation steps
• Direct effectors recruited by KIF20B at the constriction site unknown
• Motor-dependence of Shootin1 transport not directly demonstrated