Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells

Janisch, K; McNeely, Katrina C.; Dardick, Joseph; Lim, Samuel H; Dwyer, Noelle D.

doi:10.1091/mbc.e17-08-0495

Cited by 41 publications

(59 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As SAC does not affect shKIF20B‐induced mitotic and proliferation inhibition, and KIF20B plays a critical role in cytokinesis, consequently, we investigated at which mitotic phase shKIF20B suppressed HCC cells. First, we synchronized HepG2 cells at M‐phase by VX‐680 and measured the length of mitosis by checking the phosphorylation level of histone H3 (p‐H3), an M‐phase indicator .…”

Section: Resultsmentioning

confidence: 99%

“…11 KIF20B is a microtubule-associated protein specifically phosphorylated at M-phase and plays a critical role in cytokinesis. 12 In addition to its physiological roles in mitosis, KIF20B has also been found to play roles in solid tumors such as breast and bladder cancers. 13,14 Recently, we also reported the oncogenic role of KIF20B in HCC.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule‐targeting agents by blocking cytokinesis

Liu

Zhang

et al. 2018

Cancer Science

View full text Add to dashboard Cite

Kinesin family member 20B (KIF20B, also known as MPHOSPH1) is a kinesin protein that plays a critical role in cytokinesis. Previously, we and others have demonstrated the oncogenic role of KIF20B in several cancers; however, the exact mechanisms underlying its tumorigenic effects remain unclear. Herein, we showed overexpression of KIF20B in human hepatocellular carcinoma (HCC) and reported a negative correlation between KIF20B level and prognosis of patients. Mechanistically, reducing KIF20B blockades mitotic exit of HCC cells at telophase in a spindle assembly checkpoint independent way. Importantly, reducing KIF20B acts synergistically with three microtubule‐associated agents (MTA) to p53‐ or p14ARF‐dependently suppress p53‐wt or p53‐null HCC cells. In addition to taxol, reducing KIF20B also enhanced the toxicity of two chemotherapeutic drugs, hydroxycamptothecin and mitomycin C. In conclusion, we found a novel mechanism in that blocking cytokinesis by KIF20B inhibition increases the efficacy of MTA; our results thus suggested a dual‐mitotic suppression approach against HCC by combining MTA with KIF20B inhibition, which simultaneously blocks mitosis at both metaphase and telophase.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule‐targeting agents by blocking cytokinesis

Liu

Zhang

et al. 2018

Cancer Science

View full text Add to dashboard Cite

show abstract

“…Previously, we showed that a loss-of-function mutation of the Kinesin-6 Kif20b in mice causes microcephaly (25,26). Kif20b protein localizes to the central spindle during furrowing, then to midbody flanks and finally to the constriction sites ( Figure 1G and (27,28). This dynamic localization during cytokinesis, suggests that Kif20b could play important roles in furrowing or abscission.…”

Section: Introductionmentioning

confidence: 75%

“…This dynamic localization during cytokinesis, suggests that Kif20b could play important roles in furrowing or abscission. We showed that in HeLa cells, Kif20b depletion caused subtle disruptions of furrowing speed, midbody maturation and abscission timing, but does not prevent abscission completion (27). This raised the question of whether Kif20b loss in NSCs would cause more severe defects in cytokinesis.…”

Section: Introductionmentioning

confidence: 98%

Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging

McNeely

Little²,

Dwyer

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Building a brain of the proper size and structure requires neural stem cells (NSCs) to divide with tight temporal and spatial control to produce different daughter cell types in proper numbers and sequence. Mammalian NSCs in the embryonic cortex must maintain their polarized epithelial structure as they undergo both early proliferative divisions and later neurogenic divisions. To do this they undergo a polarized form of cytokinesis at the apical membrane that is not well understood. Here we investigate whether polarized furrowing and abscission in mouse NSCs are regulated differently at earlier and later stages, and in a cytokinesis mutant, Kif20b. We developed methods to live image furrow ingression and midbody microtubule abscission in NSCs within cortical explants. We find that polarized furrow ingression occurs at a steady rate and completes in 15 minutes, regardless of developmental age. However, ingression is slowed in a subset of Kif20b mutant NSCs. Abscission is usually observed on both midbody flanks, and takes 65-75 minutes to complete. Surprisingly, the process is accelerated in the microcephalic Kif20b mutant NSCs. Midbody remnants litter the apical membrane surface, and are more prevalent with early proliferative divisions. These results suggest that abscission is developmentally regulated in NSCs and may influence proper brain growth and structure.

show abstract

“…This method was previously described in (McNeely & Dwyer, 2020), based on first establishing SiR-tubulin for abscission duration studies in HeLa cells (Janisch et al, 2018). Briefly, E13.5 slabs were prepared as described above and placed apical surface down in a glass-bottom dish (MatTek, Ashland, MA, P35G-1.0–20-C) containing 50 nM SiR-Tubulin (Cytoskeleton, Denver, CO CY-SC002) in Final Culture Medium (described above).…”

Section: Methodsmentioning

confidence: 99%

Loss of coiled-coil protein Cep55 impairs abscission processes and results in p53-dependent apoptosis in developing cortex

Little

McNeely

Michel

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

13To produce a brain of normal size and structure, embryonic neural stem cell (NSCs) must tightly regulate 14 their cell divisions. Cerebral cortex NSCs undergo a polarized form of cytokinesis whose regulation is 15 poorly understood. Cytokinetic abscission severs the daughter cells and is mediated by the midbody at the 16 apical membrane. Here we elucidate the role of the coiled-coil midbody protein Cep55 in NSC abscission 17 and brain development. A knockout of Cep55 in mice causes microcephaly with reduced NSCs and 18 neurons, but relatively normal body size. Fixed and live analyses show NSCs lacking Cep55 have 19 decreased but not eliminated ESCRT recruitment, and have abnormal abscission and higher rates of 20 failure. P53-mediated apoptosis is greatly increased in the brain, but not other tissues, and p53 knockout 21 partly rescues brain size. Thus, loss of Cep55 causes abscission defects and failures in multiple cell types, 22 but the secondary p53 response and apoptosis is brain-specific. 23 24 65 caused almost universal failure of cell division (Fabbro et al., 2005; Zhao et al., 2006). 66Here, we use a mouse knockout to elucidate the roles and requirements of Cep55 in abscission of 67 neural stem cells during brain development. We find Cep55 is not absolutely required for abscission in 68 NSCs or other embryonic cells, but its loss causes abnormalities and increases failures. NSCs are 69 especially vulnerable to loss of Cep55 compared to other tissues, and brain size is disproportionally 70 2 reduced. Surprisingly, we find ESCRT recruitment is not eliminated in Cep55 -/-cell midbodies, though 71 it is impaired. We use fixed and live imaging of intact cortical epithelium to probe Cep55's role in 72 abscission. Additionally, we find the severe effect on the nervous system compared to other tissues 73 appears to be due to a specific p53 response triggering apoptosis, and test this using double knockout of 74 Cep55 and p53. This work underlines that studying cytokinetic proteins and processes in the context of 75 developing tissues is necessary to complement single cell models, in order to understand both the cellular 76 roles of specific proteins, and how their loss can cause various phenotypes at the tissue and organism 77 level. 78 79 Results 80 81 Cep55 knockout results in microcephaly with thin neuronal and axonal layers 82 83 The mutation of Cep55 used in this analysis is a 600 base-pair deletion encompassing all of exon 84 6 and flanking intronic sequence, generated by the CMMR (see Methods). The total murine Cep55 gene 85 consists of 9 exons encoding a protein of 462 amino acids (AA) (Figure 1A). Cep55 protein domains 86 include two coiled-coil regions (CC1 and CC2) surrounding the ESCRT-and Alix-binding region 87 (EABR), and two ubiquitin binding domains (UBD) in the C-terminus (Lee et al., 2008; Morita et al., 88 2007; Said Halidi et al., 2019). This deletion is predicted to result in a frameshift starting at AA 227, 89 resulting in multiple premature stop codons starting after AA 237. The Cep55 pr...

show abstract

Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells

Cited by 41 publications

References 57 publications

Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule‐targeting agents by blocking cytokinesis

Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule‐targeting agents by blocking cytokinesis

Cytokinetic furrowing and abscission dynamics during brain development revealed by live imaging

Loss of coiled-coil protein Cep55 impairs abscission processes and results in p53-dependent apoptosis in developing cortex

Contact Info

Product

Resources

About