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

被引：10

作者：

Jensen, Amornrat Naranuntarat ^{[1
]}

Chindaudomsate, Worathad ^{[2
]}

Thitiananpakorn, Kanate ^{[3
]}

Mongkolsuk, Skorn ^{[4
]}

Jensen, Laran T. ^{[2
]}

机构：

[1] Mahidol Univ, Dept Pathobiol, Fac Sci, Bangkok 10400, Thailand

[2] Mahidol Univ, Dept Biochem, Fac Sci, Bangkok 10400, Thailand

[3] Mahidol Univ, Toxicol Grad Program, Fac Sci, Bangkok 10400, Thailand

[4] Mahidol Univ, Dept Biotechnol, Fac Sci, Bangkok 10400, Thailand

来源：

FEBS LETTERS | 2014年 / 588卷 / 21期

关键词：

Artemisinin; Malaria; Lysine deacetylase; RPD3; Protein trafficking; Saccharomyces cerevisiae; HISTONE DEACETYLASE; SACCHAROMYCES-CEREVISIAE; PLASMODIUM-FALCIPARUM; ANTIMALARIAL ACTIVITY; MULTIDRUG-RESISTANCE; COMBINATION THERAPY; HDAC INHIBITORS; DOWN-REGULATION; IN-VIVO; YEAST;

D O I：

10.1016/j.febslet.2014.09.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 Delta mutants with impaired endoplasmic reticulum (ER) to Golgi protein trafficking. Decreased accumulation of the transporters Pdr5p, Fur4p, and Tat2p was observed in rpd3 Delta and sit4 Delta cells. The unfolded protein response is induced in rpd3 Delta 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. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：4018 / 4025

页数：8

共 83 条

[1] Novel Inhibitor of Plasmodium Histone Deacetylase That Cures P. berghei-Infected Mice [J].

Agbor-Enoh, S. ;

Seudieu, C. ;

Davidson, E. ;

Dritschilo, A. ;

Jung, M. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2009, 53 (05) :1727-1734

[2] The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress [J].

Alejandro-Osorio, Adriana L. ;

Huebert, Dana J. ;

Porcaro, Dominic T. ;

Sonntag, Megan E. ;

Nillasithanukroh, Songdet ;

Lwill, Jessica ;

Gasch, Audrey P. .

GENOME BIOLOGY, 2009, 10 (05)

[3] Adaptive response to the antimalarial drug artesunate in yeast involves Pdr1p/Pdr3p-mediated transcriptional activation of the resistance determinants TPO1 and PDR5 [J].

Alenquer, Marta ;

Tenreiro, Sandra ;

Sa-Correia, Isabel .

FEMS YEAST RESEARCH, 2006, 6 (08) :1130-1139

[4] Potent antimalarial activity of histone deacetylase inhibitor analogues [J].

Andrews, K. T. ;

Tran, T. N. ;

Lucke, A. J. ;

Kahnberg, P. ;

Le, G. T. ;

Boyle, G. M. ;

Gardiner, D. L. ;

Skinner-Adams, T. S. ;

Fairlie, D. P. .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (04) :1454-1461

[5] HDAC inhibitors in parasitic diseases [J].

Andrews, Katherine T. ;

Haque, Ashraful ;

Jones, Malcolm K. .

IMMUNOLOGY AND CELL BIOLOGY, 2012, 90 (01) :66-77

[6] Anti-malarial effect of histone deacetylation inhibitors and mammalian tumour cytodifferentiating agents [J].

Andrews, KT ;

Walduck, A ;

Kelso, MJ ;

Fairlie, DP ;

Saul, A ;

Parsons, PG .

INTERNATIONAL JOURNAL FOR PARASITOLOGY, 2000, 30 (06) :761-768

[7]

[Anonymous], 1979, CHINESE MED J-PEKING, V92, P811

[8] Histone modifications in transcriptional regulation [J].

Berger, SL .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2002, 12 (02) :142-148

[9] Sit4p/PP6 regulates ER-to-Golgi traffic by controlling the dephosphorylation of COPII coat subunits [J].

Bhandari, Deepali ;

Zhang, Jinzhong ;

Menon, Shekar ;

Lord, Christopher ;

Chen, Shuliang ;

Helm, Jared R. ;

Thorsen, Kevin ;

Corbett, Kevin D. ;

Hay, Jesse C. ;

Ferro-Novick, Susan .

MOLECULAR BIOLOGY OF THE CELL, 2013, 24 (17) :2727-2738

[10] An aspartyl protease directs malaria effector proteins to the host cell [J].

Boddey, Justin A. ;

Hodder, Anthony N. ;

Guenther, Svenja ;

Gilson, Paul R. ;

Patsiouras, Heather ;

Kapp, Eugene A. ;

Pearce, J. Andrew ;

de Koning-Ward, Tania F. ;

Simpson, Richard J. ;

Crabb, Brendan S. ;

Cowman, Alan F. .

NATURE, 2010, 463 (7281) :627-U52

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