Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors

Masashi Yukawa, Tomoaki Yamauchi, Ken-ichi Kimura, View ORCID ProfileTakashi Toda
doi: https://doi.org/10.1101/257436
Masashi Yukawa
aHiroshima Research Center for Healthy Aging
bLaboratory of Molecular and Chemical Cell Biology, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: myukawa@hiroshima-u.ac.jp takashi-toda@hiroshima-u.ac.jp
Tomoaki Yamauchi
bLaboratory of Molecular and Chemical Cell Biology, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ken-ichi Kimura
cChemical Biology Laboratory, The United Graduate School of Agricultural Sciences, Graduate School of Agriculture, and Faculty of Agriculture, Iwate University, Morioka, Iwate 020-8550, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Toda
aHiroshima Research Center for Healthy Aging
bLaboratory of Molecular and Chemical Cell Biology, Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Takashi Toda
  • For correspondence: myukawa@hiroshima-u.ac.jp takashi-toda@hiroshima-u.ac.jp
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Many cancer cells contain more than two centrosomes, yet these cancer cells can form bipolar spindles and appear to proliferate normally, instead of committing lethal mitoses with multipolar spindles. It is shown that extra centrosomes are clustered into two pseudo-bipolar spindle poles, thereby escaping from multipolarity. Human kinesin-14 (HSET or KIFC1), a minus end-directed motor, plays a crucial role in centrosome clustering and as such, HSET is essential for cell viability only in cancer cells with supernumerary centrosomes, but not in non-transformed cells. Accordingly, HSET is deemed to be an efficient chemotherapeutic target to selectively kill cancer cells. Recently, three HSET inhibitors (AZ82, CW069 and SR31527) have been reported, but their specificity, efficacy and off-target cytotoxicity have not been evaluated rigorously. Here we show that these inhibitors on their own are cytotoxic to fission yeast, suggesting that they have other targets in vivo except for kinesin-14. Nonetheless, intriguingly, AZ82 can neutralize overproduced HSET and partially rescue its lethality. This methodology of protein overproduction in fission yeast provides a convenient, functional assay system by which to screen for not only selective human kinesin-14 inhibitors but also those against other molecules of interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted February 05, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors
Masashi Yukawa, Tomoaki Yamauchi, Ken-ichi Kimura, Takashi Toda
bioRxiv 257436; doi: https://doi.org/10.1101/257436
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Fission yeast cells overproducing HSET/KIFC1 provides a useful tool for identification and evaluation of human kinesin-14 inhibitors
Masashi Yukawa, Tomoaki Yamauchi, Ken-ichi Kimura, Takashi Toda
bioRxiv 257436; doi: https://doi.org/10.1101/257436

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4838)
  • Biochemistry (10729)
  • Bioengineering (8006)
  • Bioinformatics (27168)
  • Biophysics (13930)
  • Cancer Biology (11079)
  • Cell Biology (15984)
  • Clinical Trials (138)
  • Developmental Biology (8757)
  • Ecology (13228)
  • Epidemiology (2067)
  • Evolutionary Biology (17307)
  • Genetics (11663)
  • Genomics (15877)
  • Immunology (10986)
  • Microbiology (25979)
  • Molecular Biology (10600)
  • Neuroscience (56312)
  • Paleontology (416)
  • Pathology (1727)
  • Pharmacology and Toxicology (2998)
  • Physiology (4528)
  • Plant Biology (9583)
  • Scientific Communication and Education (1610)
  • Synthetic Biology (2668)
  • Systems Biology (6956)
  • Zoology (1507)