Liang, Ying Yu, Bacanu, Smaranda, Sreekumar, Lekshmy, Ramos, Anderson Daniel, Dai, Lingyun, Michaelis, Martin, Cinatl, Jindrich, Seki, Takahiro, Cao, Yihai, Coffill, Cynthia R., and others. (2021) CETSA interaction proteomics define specific RNA-modification pathways as key components of fluorouracil-based cancer drug cytotoxicity. Cell Chemical Biology, . E-ISSN 2451-9456. (doi:10.1016/j.chembiol.2021.06.007) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:90383)
| The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication) | |
| Official URL: https://doi.org/10.1016/j.chembiol.2021.06.007 |
Abstract
The optimal use of many cancer drugs is hampered by a lack of detailed understanding of their mechanism of action (MoA). Here, we apply a high-resolution implementation of the proteome-wide cellular thermal shift assay (CETSA) to follow protein interaction changes induced by the antimetabolite 5-fluorouracil (5-FU) and related nucleosides. We confirm anticipated effects on the known main target, thymidylate synthase (TYMS), and enzymes in pyrimidine metabolism and DNA damage pathways. However, most interaction changes we see are for proteins previously not associated with the MoA of 5-FU, including wide-ranging effects on RNA-modification and -processing pathways. Attenuated responses of specific proteins in a resistant cell model identify key components of the 5-FU MoA, where intriguingly the abrogation of TYMS inhibition is not required for cell proliferation.
| Item Type: | Article |
|---|---|
| DOI/Identification number: | 10.1016/j.chembiol.2021.06.007 |
| Uncontrolled keywords: | drug mechanism of action; drug resistance; CETSA; cellular thermal shift assay; proteomics; cancer; 5-fluorouracil |
| Subjects: |
R Medicine > RC Internal medicine > RC254 Neoplasms. Tumors. Oncology R Medicine > RM Therapeutics. Pharmacology |
| Divisions: | Divisions > Division of Natural Sciences > Biosciences |
| Depositing User: | Martin Michaelis |
| Date Deposited: | 27 Sep 2021 17:45 UTC |
| Last Modified: | 14 Nov 2022 23:13 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/90383 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Michaelis, Martin.
| Creator's ORCID: |
 https://orcid.org/0000-0002-5710-5888
|
|---|---|
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