Kinesin-5 inhibitor resistance is driven by kinesin-12

The kinesin-5 Eg5 is essential for mitotic progression, and the lethal effects of Eg5 inhibitors make these inhibitors attractive candidates for chemotherapy drugs. Sturgill et al. show that kinesin-12 and a nonmotile Eg5 mutant form an alternative spindle assembly pathway that provides resistance to Eg5 inhibitors.

• Publication year

  2016

• Venue

  Journal of Cell Biology

• Publication date

  2016-04-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.201507036PMID 27091450PMCID 5084272
• 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.

• Influence of fluorescent tag on the motility properties of kinesin-1 in single-molecule assays.

  2015influential reference
• Measuring Pushing and Braking Forces Generated by Ensembles of Kinesin-5 Crosslinking Two Microtubules.

  2015cited by this paper
• Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes

  2015cited by this paper
• Kinesin-5 is a microtubule polymerase

  2015cited by this paper
• The Kinesin-12 Kif15 is a processive track-switching tetramer

  2014cited by this paper
• Multi-perspective quality control of Illumina exome sequencing data using QC3.

  2014influential reference
• Three-stage quality control strategies for DNA re-sequencing data

  2014influential reference
• MultiRankSeq: Multiperspective Approach for RNAseq Differential Expression Analysis and Quality Control

  2014influential reference
• Kinesin-12 Kif15 targets kinetochore fibers through an intrinsic two-step mechanism.

  2014influential reference
• Advanced Heat Map and Clustering Analysis Using Heatmap3

  2014cited by this paper
• Synergism between inhibitors of Aurora A and KIF11 overcomes KIF15‐dependent drug resistance

  2014influential reference
• DrugTargetSeqR: a genomics- and CRISPR/Cas9-based method to analyze drug targets

  2014cited by this paper
• Dimerization of mammalian kinesin-3 motors results in superprocessive motion

  2014cited by this paper
• Eg5 restricts anaphase B spindle elongation in mammalian cells

  2014cited by this paper
• TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions

  2013cited by this paper
• RNA-Guided Human Genome Engineering via Cas9

  2013influential reference
• The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line

  2013cited by this paper
• Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks

  2012cited by this paper
• Nuclear envelope‐associated dynein drives prophase centrosome separation and enables Eg5‐independent bipolar spindle formation

  2012influential reference
• Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration

  2012cited by this paper
• Kinesins and cancer

  2012influential reference
• Using transcriptome sequencing to identify mechanisms of drug action and resistance

  2011cited by this paper
• Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake

  2011cited by this paper
• A framework for variation discovery and genotyping using next-generation DNA sequencing data

  2011cited by this paper
• Streamlined platform for short hairpin RNA interference and transgenesis in cultured mammalian cells

  2011influential reference
• Regulated degradation of spindle assembly factors by the anaphase-promoting complex.

  2010cited by this paper
• Microtubule organization by the antagonistic mitotic motors kinesin-5 and kinesin-14

  2010cited by this paper
• Motile microtubule crosslinkers require distinct dynamic properties for correct functioning during spindle organization in Xenopus egg extract

  2009cited by this paper
• The role of Hklp2 in the stabilization and maintenance of spindle bipolarity.

  2009influential reference
• Kif15 cooperates with eg5 to promote bipolar spindle assembly.

  2009influential reference
• A novel small-molecule inhibitor reveals a possible role of kinesin-5 in anastral spindle-pole assembly

  2008cited by this paper
• XMAP215 is a processive microtubule polymerase.

  2008cited by this paper
• Discovery and biochemical characterization of selective ATP competitive inhibitors of the human mitotic kinesin KSP.

  2008cited by this paper
• Mechanism of inhibition of human KSP by ispinesib.

  2008cited by this paper
• Kinesin-5 acts as a brake in anaphase spindle elongation.

  2007cited by this paper
• Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array

  2007cited by this paper
• Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p

  2007influential reference
• Small-molecule and mutational analysis of allosteric Eg5 inhibition by monastrol

  2006cited by this paper
• Dimeric Eg5 Maintains Processivity through Alternating-site Catalysis with Rate-limiting ATP Hydrolysis*

  2006cited by this paper
• Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1.

  2006cited by this paper
• Kinesin spindle protein (KSP) inhibitors. Part 1: The discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of the mitotic kinesin KSP.

  2005cited by this paper
• The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks

  2005cited by this paper
• Cell cycle-dependent dynamics and regulation of mitotic kinesins in Drosophila S2 cells.

  2005cited by this paper
• Theoretical and practical advances in genome halving

  2004cited by this paper
• The rate of bipolar spindle assembly depends on the microtubule-gliding velocity of the mitotic kinesin Eg5.

  2004cited by this paper
• Identification of the protein binding region of S-trityl-L-cysteine, a new potent inhibitor of the mitotic kinesin Eg5.

  2004cited by this paper
• The kinesin Eg5 drives poleward microtubule flux in Xenopus laevis egg extract spindles

  2004cited by this paper
• In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities.

  2004cited by this paper
• hNuf2 inhibition blocks stable kinetochore–microtubule attachment and induces mitotic cell death in HeLa cells

  2002cited by this paper
• Targeting the kinesin Eg5 to monitor siRNA transfection in mammalian cells.

  2002cited by this paper
• Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells

  2002cited by this paper
• A structural change in the kinesin motor protein that drives motility

  1999influential reference
• Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping.

  1999cited by this paper
• A simple method for analyzing microsatellite allele image patterns generated from DNA pools and its application to allelic association studies.

  1998cited by this paper
• A bipolar kinesin

  1996cited by this paper
• Mutations in the kinesin-like protein Eg5 disrupting localization to the mitotic spindle.

  1995cited by this paper
• Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo.

  1995cited by this paper
• Mitotic spindle organization by a plus-end-directed microtubule motor

  1992cited by this paper

• Kinesin Spindle Protein (KIF11) in Mitosis and Cancer

  2025cites this paper
• The multifaceted role of KIF15 in cancer progression and therapy

  2025influential citation
• Targeting Kinesins for Therapeutic Exploitation of Chromosomal Instability in Lung Cancer

  2025cites this paper
• Systematic Identification of Microtubule Posttranslational Modification "Readers" by Quantitative Proteomics.

  2025cites this paper
• Cancer on motors: How kinesins drive prostate cancer progression?

  2024cites this paper
• Antiparallel microtubule bundling supports KIF15-driven mitotic spindle assembly

  2024cites this paper
• Mechanism and regulation of kinesin motors

  2024cites this paper
• Microtubule choreography: spindle self-organization during cell division

  2024cites this paper
• Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

  2024cites this paper
• KIF15 promotes the development and progression of chordoma via activating PI3K-AKT signalling pathway

  2024cites this paper
• Positioning centrioles and centrosomes

  2024cites this paper
• Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells

  2024cites this paper
• Mechanisms underlying spindle assembly and robustness

  2023cites this paper
• Liposomal nanocarriers containing siRNA as small molecule-based drugs to overcome cancer drug resistance.

  2023cites this paper
• Modification of the neck-linker of KIF18A alters Microtubule subpopulation preference

  2023cites this paper
• Modification of the Neck Linker of KIF18A Alters Microtubule Subpopulation Preference

  2023cites this paper
• Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells

  2023cites this paper
• Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma

  2023cites this paper
• Kinesin-5 Eg5 mediates centrosome separation to control spindle assembly in spermatocytes

  2022influential citation
• Chemical Biology of Mitotic Spindle Assembly Motors.

  2022cites this paper
• Drug resistance dependent on allostery: A P-loop rigor Eg5 mutant exhibits resistance to allosteric inhibition by STLC

  2022influential citation
• Synergy between inhibitors of two mitotic spindle assembly motors undermines an adaptive response

  2022cites this paper
• Kinesin KIF15 regulates tubulin acetylation and spindle assembly checkpoint in mouse oocyte meiosis

  2022cites this paper
• Combined inhibition of KIF11 and KIF15 as an effective therapeutic strategy for gastric cancer.

  2022cites this paper
• Kinesin family member 15 can promote the proliferation of glioblastoma.

  2022influential citation
• Optical tweezers across scales in cell biology.

  2022cites this paper
• Acentrosomal spindle assembly and maintenance in Caenorhabditis elegans oocytes requires a kinesin-12 nonmotor microtubule interaction domain

  2022cites this paper
• Activation of STAT3 through combined SRC and EGFR signaling drives resistance to a mitotic kinesin inhibitor in glioblastoma

  2022cites this paper
• KIF15 is involved in development and progression of Burkitt lymphoma

  2021cites this paper
• KIF15 expression characteristics: Relevance toneo-adjuvant chemotherapy efficacy in breast cancer

  2021cites this paper
• Multiple motors cooperate to establish and maintain acentrosomal spindle bipolarity in C. elegans oocyte meiosis

  2021cites this paper
• KIF15 upregulation promotes leiomyosarcoma cell growth via promoting USP15-mediated DEK deubiquitylation.

  2021cites this paper
• Mechanisms by Which Kinesin-5 Motors Perform Their Multiple Intracellular Functions

  2021cites this paper
• Acentrosomal spindle assembly and stability in C. elegans oocytes requires a kinesin-12 non-motor microtubule interaction domain

  2021cites this paper
• Measuring force generation within reconstituted microtubule bundle assemblies using optical tweezers

  2021cites this paper
• Chemical tools for dissecting cell division

  2021cites this paper
• Pathogenic mutations in the chromokinesin KIF22 disrupt anaphase chromosome segregation

  2021cites this paper
• How Essential Kinesin-5 Becomes Non-Essential in Fission Yeast: Force Balance and Microtubule Dynamics Matter

  2020cites this paper
• The kinesin-5 tail domain directly modulates the mechanochemical cycle of the motor domain for anti-parallel microtubule sliding

  2020cites this paper
• A mouse model for Kinesin Family Member 11 (Kif11)-associated familial exudative vitreoretinopathy.

  2020cites this paper
• KSP siRNA/paclitaxel-loaded PEGylated cationic liposomes for overcoming resistance to KSP inhibitors: Synergistic antitumor effects in drug-resistant ovarian cancer.

  2020cites this paper
• Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy

  2020cites this paper
• Kinesin-5 Eg5 is essential for spindle assembly and chromosome alignment of mouse spermatocytes

  2020cites this paper
• KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors

  2020cites this paper
• Identification of KIF15 as a potential therapeutic target and prognostic factor for glioma

  2020cites this paper
• KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

  2020cites this paper
• How Essential Kinesin-5 Becomes Non-Essential: Force Balance and Microtubule Dynamics Matter

  2020cites this paper
• Chromosomally unstable tumor cells specifically require KIF18A for proliferation

  2020cites this paper
• CRISPR/Cas9 in Cancer Immunotherapy: Animal Models and Human Clinical Trials

  2020cites this paper
• Profilin choreographs actin and microtubules in cells and cancer.

  2020cites this paper
• HSP70 regulates Eg5 distribution within the mitotic spindle and modulates the cytotoxicity of Eg5 inhibitors

  2020cites this paper
• Eg5 Targeting Agents : From new anti-mitotic based inhibitor discovery to cancer therapy and resistance.

  2020cites this paper
• Parthenolide Destabilizes Microtubules by Covalently Modifying Tubulin.

  2020cites this paper
• Mechanism of microtubule-trapped human kinesin-5 inhibition revealed using cryo-EM

  2020cites this paper
• Kinesin-5 Regulation and Function in Mitosis.

  2019cites this paper
• KIF15 promotes bladder cancer proliferation via the MEK–ERK signaling pathway

  2019cites this paper
• KIF15 plays a role in promoting the tumorigenicity of melanoma.

  2019cites this paper
• Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15

  2019cites this paper
• The balance of forces generated by kinesins controls spindle polarity and chromosomal heterogeneity in tetraploid cells

  2019cites this paper
• Dual inhibition of Kif15 by oxindole and quinazolinedione chemical probes.

  2019cites this paper
• Identification of Potential Biomarkers in Association With Progression and Prognosis in Epithelial Ovarian Cancer by Integrated Bioinformatics Analysis

  2019cites this paper
• Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5–Inhibitor Complexes

  2019cites this paper
• The conditional nature of gene essentiality.

  2019cites this paper
• The Kinesin-5 Tail Domain Directly Modulates the Mechanochemical Cycle of the Motor for Anti-Parallel Microtubule Sliding

  2019cites this paper
• Regulation and Pharmacology of the Mitotic Kinesin Kif15

  2019influential citation
• Identification of key biomarkers associated with development and prognosis in patients with ovarian carcinoma: evidence from bioinformatic analysis

  2019cites this paper
• Structural organisation of the human kinesin-12 Kif15

  2018cites this paper
• Human CLASP2 specifically regulates microtubule catastrophe and rescue

  2018cites this paper
• VPS28, an ESCRT-I protein, regulates mitotic spindle organization via Gβγ, EG5 and TPX2.

  2018cites this paper
• Motor Protein Regulation in Mammalian Mitosis

  2018influential citation
• Kinesin-Binding Protein (KBP) buffers the activity of KIF18A and KIF15 in mitosis to ensure accurate chromosome segregation

  2018cites this paper
• Involvement of C-terminal truncation mutation of kinesin-5 in resistance to kinesin-5 inhibitor

  2018cites this paper
• Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9‐mediated kif15 mutations accelerate axonal outgrowth during neuronal development and regeneration in zebrafish

  2018cites this paper
• Distribution of Eg5 and TPX2 in mitosis: Insight from CRISPR tagged cells

  2018cites this paper
• Processive Kinesin-14 HSET Exhibits Directional Flexibility Depending on Motor Traffic.

  2018cites this paper
• Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters

  2018cites this paper
• Altered chemomechanical coupling causes impaired motility of the kinesin-4 motors KIF27 and KIF7

  2018cites this paper
• Kif15 functions as an active mechanical ratchet

  2018cites this paper
• KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics

  2018cites this paper
• Altered chemomechanical coupling causes impaired motility of the kinesin-4 motors KIF27 and KIF7

  2018cites this paper
• Mitotic spindle assembly in animal cells: a fine balancing act

  2017cites this paper
• Clinical Development of Anti-mitotic Drugs in Cancer.

  2017cites this paper
• Metaphase Spindle Assembly

  2017cites this paper
• Cell Division: Centrosomes Have Separation Anxiety.

  2017cites this paper
• Kinesin-5-independent mitotic spindle assembly requires the antiparallel microtubule crosslinker Ase1 in fission yeast

  2017cites this paper
• Structural basis of human kinesin-8 function and inhibition

  2017influential citation
• Collective Force Regulation in Anti-parallel Microtubule Gliding by Dimeric Kif15 Kinesin Motors.

  2017influential citation
• Eg5 Inhibitors Have Contrasting Effects on Microtubule Stability and Metaphase Spindle Integrity.

  2017cites this paper
• KIF15 promotes pancreatic cancer proliferation via the MEK–ERK signalling pathway

  2017cites this paper
• Anti‐mitotic agents: Are they emerging molecules for cancer treatment?☆

  2017cites this paper
• Two mechanisms coordinate the recruitment of the chromosomal passenger complex to the plane of cell division

  2017cites this paper
• Regulation of Kif15 localization and motility by the C-terminus of TPX2 and microtubule dynamics

  2017influential citation
• Resistance is not futile: Surviving Eg5 inhibition

  2016cites this paper
• Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation

  2016cites this paper
• Assembly of Caenorhabditis elegans acentrosomal spindles occurs without evident microtubule-organizing centers and requires microtubule sorting by KLP-18/kinesin-12 and MESP-1

  2016cites this paper
• Expression and correlation of PIM -1 and Eg5 proteins in prostate cancer

  year unknowncites this paper