Improper protein trafficking contributes to artemisinin sensitivity in cells lacking the KDAC Rpd3p.

Autor: Jensen AN; Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand., Chindaudomsate W; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand., Thitiananpakorn K; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand., Mongkolsuk S; Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand., Jensen LT; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand. Electronic address: laran.jen@mahidol.ac.th.
Jazyk: angličtina
Zdroj: FEBS letters [FEBS Lett] 2014 Nov 03; Vol. 588 (21), pp. 4018-25. Date of Electronic Publication: 2014 Sep 27.
DOI: 10.1016/j.febslet.2014.09.021
Abstrakt: Lysine deacetylases (KDACs) inhibitors may have therapeutic value in anti-malarial combination therapies with artemisinin. To evaluate connections between KDACs and artemisinin, Saccharomyces cerevisiae deletion mutants in KDAC genes were assayed. Deletion of RPD3, but not other KDAC genes, resulted in strong sensitivity to artemisinin, which was also observed in sit4Δ mutants with impaired endoplasmic reticulum (ER) to Golgi protein trafficking. Decreased accumulation of the transporters Pdr5p, Fur4p, and Tat2p was observed in rpd3Δ and sit4Δ cells. The unfolded protein response is induced in rpd3Δ cells consistent with retention of proteins in the ER. Disruption of protein trafficking appears to sensitize cells to artemisinin and targeting these pathways may be useful as part of artemisinin based anti-malarial therapy.
(Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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