Non-motor Spindle Proteins as Cancer Chemotherapy Targets

  • Robert L. MargolisEmail author
  • Mythili Yenjerla


The mitotic spindle consists of a highly organized fusiform array of microtubules which functions to precisely segregate chromosomes during cell division. Both motor and non-motor microtubule associated proteins (MAPs) promote the assembly and disassembly of spindle microtubules during mitosis. Non-motor proteins localize to distinct subcellular sites, such as kinetochores and centrosomes, during different phases of mitosis. They are responsible for linking spindle microtubules to the kinetochore to ensure proper chromosomal alignment during metaphase, and are required for centrosome maturation and separation. Acting together with motor proteins, the non-motor proteins thus enable the formation of the bipolar spindle with microtubules spanning from spindle poles to kinetochores and between spindle poles. At the spindle midzone, specific MAPs cause bundling of antiparallel microtubules that is a prerequisite for proper cell cleavage. Interestingly, the non-motor proteins are frequently overexpressed in different tumors. Among the anti-mitotic drugs currently in clinical use, drugs that target microtubules have been the most successful to date. An emerging class of potential chemotherapy drugs includes inhibitors of non-motor spindle proteins such as the Aurora A and B protein kinases and Polo-like kinase-1. Many non-motor microtubule associated proteins, including the KMN (KNL-1/Mis12 complex/Ndc80) and CPC (chromosome passenger complex) networks of interacting proteins, are potentially suitable as drug targets in mitosis. Drug screens must be designed to identify compounds that modify well-defined activities of the target proteins, and to interfere with completion of mitosis in tumor cells. Combination therapy, involving DNA damage followed by a mitotic second trap using drugs that target non-motor spindle proteins, could be a valuable approach when tumor cell response is differentially insensitive to DNA damage. In this chapter we describe important non-motor proteins that may serve as potential therapeutic targets.


Mitotic Spindle Aurora Kinase Spindle Pole Spindle Assembly Spindle Assembly Checkpoint 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by NIH grants R01GM068107 and R01GM088716 (R.L.M.)


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Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Tumor Initiation and Maintenance ProgramSanford-Burnham Medical Research InstituteLa JollaUSA

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