en
Scientific article
Open access
English

Tubulin Resists Degradation by Cereblon-Recruiting PROTACs

Published inCells, vol. 9, no. 5, p. 1-14; 1083
Publication date2020-04-27
First online date2020-04-27
Abstract

Dysregulation of microtubules and tubulin homeostasis has been linked to developmental disorders, neurodegenerative diseases, and cancer. In general, both microtubule-stabilizing and destabilizing agents have been powerful tools for studies of microtubule cytoskeleton and as clinical agents in oncology. However, many cancers develop resistance to these agents, limiting their utility. We sought to address this by developing a different kind of agent: tubulin-targeted small molecule degraders. Degraders (also known as proteolysis-targeting chimeras (PROTACs)) are compounds that recruit endogenous E3 ligases to a target of interest, resulting in the target’s degradation. We developed and examined several series of α- and β-tubulin degraders, based on microtubule-destabilizing agents. Our results indicate, that although previously reported covalent tubulin binders led to tubulin degradation, in our hands, cereblon-recruiting PROTACs were not efficient. In summary, while we consider tubulin degraders to be valuable tools for studying the biology of tubulin homeostasis, it remains to be seen whether the PROTAC strategy can be applied to this target of high clinical relevance.

eng
Keywords
  • PROTAC
  • Microtubule
  • Tubulin
Affiliation Not a UNIGE publication
Funding
  • NIGMS NIH HHS - [R35 GM131753]
  • Damon Runyon Cancer Research Foundation - [DRG:2279-16]
  • National Institutes of Health - [NCI R01CA218278]
  • NCI NIH HHS - [R01 CA218278]
Citation (ISO format)
GASIC, Ivana et al. Tubulin Resists Degradation by Cereblon-Recruiting PROTACs. In: Cells, 2020, vol. 9, n° 5, p. 1–14. doi: 10.3390/cells9051083
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal2073-4409
11views
1downloads

Technical informations

Creation02/20/2024 5:24:45 PM
First validation02/21/2024 1:31:33 PM
Update time02/21/2024 1:31:33 PM
Status update02/21/2024 1:31:33 PM
Last indexation02/21/2024 1:31:53 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack