Premium
Improper protein trafficking contributes to artemisinin sensitivity in cells lacking the KDAC Rpd3p
Author(s) -
Jensen Amornrat Naranuntarat,
Chindaudomsate Worathad,
Thitiananpakorn Kanate,
Mongkolsuk Skorn,
Jensen Laran T.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.09.021
Subject(s) - artemisinin , endoplasmic reticulum , mutant , microbiology and biotechnology , unfolded protein response , golgi apparatus , lysine , saccharomyces cerevisiae , gene , biology , chemistry , biochemistry , plasmodium falciparum , amino acid , malaria , immunology
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 sit4 Δ mutants with impaired endoplasmic reticulum (ER) to Golgi protein trafficking. Decreased accumulation of the transporters Pdr5p, Fur4p, and Tat2p was observed in rpd3 Δ and sit4 Δ cells. The unfolded protein response is induced in rpd3 Δ 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.