Synergy between inhibitors of two mitotic spindle assembly motors undermines an adaptive response-Reference-Cited by-同舟云学术

Synergy between inhibitors of two mitotic spindle assembly motors undermines an adaptive response

Published:2022-12-01 Issue:14 Volume:33 Page:
ISSN:1059-1524
Container-title:Molecular Biology of the Cell
language:en
Short-container-title:MBoC

Author:

Solon April L.¹^ORCID,Zaniewski Taylor M.²,O’Brien Patrick³,Clasby Martin³,Hancock William O.⁴,Ohi Ryoma¹

Affiliation:

1. Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109

2. Department of Chemistry, Pennsylvania State University, University Park, PA 16802

3. Vahlteich Medicinal Chemistry Core, University of Michigan, Ann Arbor, MI 48109

4. Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802

Abstract

KIF15 is a mitotic kinesin that can suppress the cytotoxic effects of inhibitors of Eg5, another mitotic motor, rendering them clinically ineffective. We identified two novel and distinct KIF15 inhibitor scaffolds. Here we characterize their potency and specificity for KIF15 and demonstrate that they prevent resistance to Eg5 inhibitors in vivo.

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

Reference38 articles.

1. Deviant Kinetochore Microtubule Dynamics Underlie Chromosomal Instability

2. K-fiber bundles in the mitotic spindle are mechanically reinforced by Kif15

3. Processivity of the Kinesin-2 KIF3A Results from Rear Head Gating and Not Front Head Gating

4. Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition

5. In vitro screening for inhibitors of the human mitotic kinesin Eg5 with antimitotic and antitumor activities

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