Translational control in Plasmodium and Toxoplasma parasites

Min Zhang, Bradley R. Joyce, William Sullivan, Victor Nussenzweig

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α~P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α~P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalEukaryotic Cell
Volume12
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Plasmodium
Toxoplasma
Parasites
Life Cycle Stages
Phosphotransferases
Phosphorylation
Communicable Disease Control
Toxoplasmosis
Eukaryotic Cells
Phosphoric Monoester Hydrolases
Malaria
Gene Expression
Messenger RNA
Genes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

Translational control in Plasmodium and Toxoplasma parasites. / Zhang, Min; Joyce, Bradley R.; Sullivan, William; Nussenzweig, Victor.

In: Eukaryotic Cell, Vol. 12, No. 2, 02.2013, p. 161-167.

Research output: Contribution to journalArticle

Zhang, Min ; Joyce, Bradley R. ; Sullivan, William ; Nussenzweig, Victor. / Translational control in Plasmodium and Toxoplasma parasites. In: Eukaryotic Cell. 2013 ; Vol. 12, No. 2. pp. 161-167.
@article{62695a3327584cf597109c096e806d8b,
title = "Translational control in Plasmodium and Toxoplasma parasites",
abstract = "The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α~P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α~P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.",
author = "Min Zhang and Joyce, {Bradley R.} and William Sullivan and Victor Nussenzweig",
year = "2013",
month = "2",
doi = "10.1128/EC.00296-12",
language = "English",
volume = "12",
pages = "161--167",
journal = "Eukaryotic Cell",
issn = "1535-9778",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Translational control in Plasmodium and Toxoplasma parasites

AU - Zhang, Min

AU - Joyce, Bradley R.

AU - Sullivan, William

AU - Nussenzweig, Victor

PY - 2013/2

Y1 - 2013/2

N2 - The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α~P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α~P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

AB - The life cycles of apicomplexan parasites such as Plasmodium spp. and Toxoplasma gondii are complex, consisting of proliferative and latent stages within multiple hosts. Dramatic transformations take place during the cycles, and they demand precise control of gene expression at all levels, including translation. This review focuses on the mechanisms that regulate translational control in Plasmodium and Toxoplasma, with a particular emphasis on the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Phosphorylation of eIF2α (eIF2α~P) is a conserved mechanism that eukaryotic cells use to repress global protein synthesis while enhancing gene-specific translation of a subset of mRNAs. Elevated levels of eIF2α~P have been observed during latent stages in both Toxoplasma and Plasmodium, indicating that translational control plays a role in maintaining dormancy. Parasite-specific eIF2α kinases and phosphatases are also required for proper developmental transitions and adaptation to cellular stresses encountered during the life cycle. Identification of small-molecule inhibitors of apicomplexan eIF2α kinases may selectively interfere with parasite translational control and lead to the development of new therapies to treat malaria and toxoplasmosis.

UR - http://www.scopus.com/inward/record.url?scp=84873179181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873179181&partnerID=8YFLogxK

U2 - 10.1128/EC.00296-12

DO - 10.1128/EC.00296-12

M3 - Article

C2 - 23243065

AN - SCOPUS:84873179181

VL - 12

SP - 161

EP - 167

JO - Eukaryotic Cell

JF - Eukaryotic Cell

SN - 1535-9778

IS - 2

ER -