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  Artemisinin inhibits NRas palmitoylation by targeting the protein acyltransferase ZDHHC6

Qiu, N., Abegg, D., Guidi, M., Gilmore, K., Seeberger, P. H., & Adibekian, A. (2021). Artemisinin inhibits NRas palmitoylation by targeting the protein acyltransferase ZDHHC6. Cell Chemical Biology, 29(3), 530-537.e7. doi:10.1016/j.chembiol.2021.07.012.

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 Creators:
Qiu, Nan, Author
Abegg, Daniel, Author
Guidi, Mara1, Author           
Gilmore, Kerry1, Author           
Seeberger, Peter H.2, Author           
Adibekian, Alexander, Author
Affiliations:
1Kerry Gilmore, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863304              
2Peter H. Seeberger - Automated Systems, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863306              

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Free keywords: chemical proteomics, protein palmitoylation, natural products, artemisinin, Ras
 Abstract: Protein S-palmitoylation is a post-translational modification that plays a crucial role in cancer cells by regulating the function and localization of oncoproteins and tumor suppressor proteins. Here, we identify artemisinin (ART), a clinically approved antimalarial endoperoxide natural product with promising anticancer activities, as an inhibitor of the ER-residing palmitoyl transferase ZDHHC6 in cancer cells using a chemoproteomic approach. We show that ART covalently binds and inhibits ZDHHC6 to reduce palmitoylation of the oncogenic protein NRas, disrupt NRas subcellular localization, and attenuate the downstream pro-proliferative signaling cascades. Our study identifies artemisinin as a non-lipid-based palmitoylation inhibitor targeting a specific palmitoyl acyltransferase and provides valuable mechanistic insights into the anticancer activity of artemisinins that are currently being studied in human clinical trials for different cancers.

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Language(s): eng - English
 Dates: 2021-08-05
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.chembiol.2021.07.012
BibTex Citekey: QIU2021
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Title: Cell Chemical Biology
Source Genre: Journal
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Publ. Info: Cell Press
Pages: - Volume / Issue: 29 (3) Sequence Number: - Start / End Page: 530 - 537.e7 Identifier: ISSN: 2451-9456