A GCN2-Like eIF2α Kinase (LdeK1) of Leishmania donovani and Its Possible Role in Stress Response

作者: Shilpa J. Rao , Shimi Meleppattu , Jayanta K. Pal

DOI: 10.1371/JOURNAL.PONE.0156032

关键词:

摘要: Translation regulation in Leishmania parasites assumes significance particularly because they encounter myriad of stresses during their life cycle. The eukaryotic initiation factor 2α (eIF2α) kinases, the well-known regulators translation higher eukaryotes have now been found to control various processes these protozoan as well. Here, we report on cloning and characterization a GCN2-like eIF2α kinase from L. donovani also its modulation nutrient starvation. We cloned donovani, which named LdeK1 validated it be functional by vitro assay. was localized cytoplasm promastigotes with five-fold expression this stage parasite compared axenic amastigotes. Phosphorylation G1-arrest observed response starvation wild-type parasites. In contrast, phosphorylation significantly impaired dominant-negative mutant stress subsequent failure bring about cell Thus, is responds phosphorylating substrate, Nutrient encountered inside vector triggers metacyclogenesis. therefore propose that global translational activation followed gut sandfly could one mechanisms retool cellular machinery required for metacyclogenesis promastigotes.

参考文章(48)
Jörg J. MÖHRLE, Yi ZHAO, Barbara WERNLI, M. Richard FRANKLIN, Barbara KAPPES, Molecular cloning, characterization and localization of PfPK4, an eIF-2alpha kinase-related enzyme from the malarial parasite Plasmodium falciparum. Biochemical Journal. ,vol. 328, pp. 677- 687 ,(1997) , 10.1042/BJ3280677
Conan Chow, Serge Cloutier, Carole Dumas, Marie-Noelle Chou, Barbara Papadopoulou, Promastigote to amastigote differentiation of Leishmania is markedly delayed in the absence of PERK eIF2alpha kinase-dependent eIF2alpha phosphorylation Cellular Microbiology. ,vol. 13, pp. 1059- 1077 ,(2011) , 10.1111/J.1462-5822.2011.01602.X
J J Chen, J M Yang, R Petryshyn, N Kosower, I M London, Disulfide bond formation in the regulation of eIF-2 alpha kinase by heme. Journal of Biological Chemistry. ,vol. 264, pp. 9559- 9564 ,(1989) , 10.1016/S0021-9258(18)60568-X
R C Wek, M Ramirez, B M Jackson, A G Hinnebusch, Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression. Molecular and Cellular Biology. ,vol. 10, pp. 2820- 2831 ,(1990) , 10.1128/MCB.10.6.2820
Sebastien Lageix, Stefan Rothenburg, Thomas E. Dever, Alan G. Hinnebusch, Enhanced interaction between pseudokinase and kinase domains in Gcn2 stimulates eIF2α phosphorylation in starved cells. PLOS Genetics. ,vol. 10, ,(2014) , 10.1371/JOURNAL.PGEN.1004326
Thomas E. Dever, Lan Feng, Ronald C. Wek, A.Mark Cigan, Thomas F. Donahue, Alan G. Hinnebusch, Phosphorylation of initiation factor 2α by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast Cell. ,vol. 68, pp. 585- 596 ,(1992) , 10.1016/0092-8674(92)90193-G
B. R. Joyce, S. F. Queener, R. C. Wek, W. J. Sullivan, Phosphorylation of eukaryotic initiation factor-2α promotes the extracellular survival of obligate intracellular parasite Toxoplasma gondii Proceedings of the National Academy of Sciences of the United States of America. ,vol. 107, pp. 17200- 17205 ,(2010) , 10.1073/PNAS.1007610107
P.A. Bates, L. Tetley, Leishmania mexicana: induction of metacyclogenesis by cultivation of promastigotes at acidic pH. Experimental Parasitology. ,vol. 76, pp. 412- 423 ,(1993) , 10.1006/EXPR.1993.1050
M. Zhang, S. Mishra, R. Sakthivel, M. Rojas, R. Ranjan, W. J. Sullivan, B. M. A. Fontoura, R. Menard, T. E. Dever, V. Nussenzweig, PK4, a eukaryotic initiation factor 2α(eIF2α) kinase, is essential for the development of the erythrocytic cycle of Plasmodium Proceedings of the National Academy of Sciences of the United States of America. ,vol. 109, pp. 3956- 3961 ,(2012) , 10.1073/PNAS.1121567109