EhMLBP is an essential constituent of the <i>Entamoeba histolytica</i> epigenetic machinery and a potential drug target

Lavi, Tal; Siman‐Tov, Rama; Ankri, Serge

doi:10.1111/j.1365-2958.2008.06258.x

Cited by 19 publications

(30 citation statements)

References 27 publications

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“…Since it has been reported that UHRF1 is significantly overexpressed in cells that are infected with the parasite Toxoplasma gondii [75], drugs that downregulate UHRF1 expression, could potentially be useful for preventing parasite proliferation and persistence in host cells. In E. histolytica and other Entamoeba spp., EhMLBP is an essential and unique protein, that is involved in the recognition and binding to methylated retroelements [25,76], and does not share any homology with any human proteins [25]. Its promise as a drug target for amoebiasis is supported by the finding that the activity of EhMLBP can be inhibited by the antitumour compound, distamycin A (IC 50 = 13 µM) [77].…”

Section: Targeting the Recognition Of Methylated Dnamentioning

confidence: 93%

“…Its promise as a drug target for amoebiasis is supported by the finding that the activity of EhMLBP can be inhibited by the antitumour compound, distamycin A (IC 50 = 13 µM) [77]. In addition, EhMLBP activity has been successfully inhibited by bacteriophages that exposed a specific peptide (Pept3) at their surface [76]. Pept3 alone is unable to inhibit the parasite's growth in culture.…”

Section: Targeting the Recognition Of Methylated Dnamentioning

confidence: 97%

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Epigenetics in The Unicellular Parasite Entamoeba Histolytica

Tovy

Ankri²

2010

Future Microbiol.

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Amoebiasis is a serious infectious disease that is caused by the unicellular parasite, Entamoeba histolytica. This parasite is mainly found in developing countries, and are named owing to its ability to destroy tissues. The molecular mechanisms that regulate the virulence of this parasite are not well understood. In recent years, an increasing interest in the epigenetic regulation of the parasite's virulence has emerged. In this article, an overview of our current knowledge about the role of DNA methylation, histone modifications and RNA-associated silencing in the biology of E. histolytica is provided. The relevance of some features of the parasite's unique epigenetic machinery to the development of new antiamoebic therapeutic molecules is discussed.

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Section: Targeting the Recognition Of Methylated Dnamentioning

confidence: 93%

Section: Targeting the Recognition Of Methylated Dnamentioning

confidence: 97%

Epigenetics in The Unicellular Parasite Entamoeba Histolytica

Tovy

Ankri²

2010

Future Microbiol.

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“…The pScramblePept3 plasmid that was previously used to express a scramble peptide fused to a NLS sequence in E.histolytica [30] was used as control. The transfection of E. histolytica trophozoites was performed as described in [52].…”

Section: Methodsmentioning

confidence: 99%

A New Nuclear Function of the Entamoeba histolytica Glycolytic Enzyme Enolase: The Metabolic Regulation of Cytosine-5 Methyltransferase 2 (Dnmt2) Activity

Tovy¹,

Tov²,

Gaentzsch

et al. 2010

PLoS Pathog

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Cytosine-5 methyltransferases of the Dnmt2 family function as DNA and tRNA methyltransferases. Insight into the role and biological significance of Dnmt2 is greatly hampered by a lack of knowledge about its protein interactions. In this report, we address the subject of protein interaction by identifying enolase through a yeast two-hybrid screen as a Dnmt2-binding protein. Enolase, which is known to catalyze the conversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), was shown to have both a cytoplasmatic and a nuclear localization in the parasite Entamoeba histolytica. We discovered that enolase acts as a Dnmt2 inhibitor. This unexpected inhibitory activity was antagonized by 2-PG, which suggests that glucose metabolism controls the non-glycolytic function of enolase. Interestingly, glucose starvation drives enolase to accumulate within the nucleus, which in turn leads to the formation of additional enolase-E.histolytica DNMT2 homolog (Ehmeth) complex, and to a significant reduction of the tRNAAsp methylation in the parasite. The crucial role of enolase as a Dnmt2 inhibitor was also demonstrated in E.histolytica expressing a nuclear localization signal (NLS)-fused-enolase. These results establish enolase as the first Dnmt2 interacting protein, and highlight an unexpected role of a glycolytic enzyme in the modulation of Dnmt2 activity.

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“…EhMLBP was induced by heat shock, and its constitutive overexpression protected trophozoites against heat shock (Katz et al 2012 ) . Treatment of E. histolytica with distamycin A, a drug-blocking EhMLBP binding to methylated LINE DNA in vitro, effectively inhibited the growth of the parasite (Lavi et al 2008 ) . In addition, E. histolytica transfectants containing a phage-expressed peptide speci fi cally binding to EhMLBP also impaired the growth of trophozoites (Lavi et al 2008 ) .…”

Section: Entamoeba Histolytica -Methylated Line-binding Proteinmentioning

confidence: 98%

“…Treatment of E. histolytica with distamycin A, a drug-blocking EhMLBP binding to methylated LINE DNA in vitro, effectively inhibited the growth of the parasite (Lavi et al 2008 ) . In addition, E. histolytica transfectants containing a phage-expressed peptide speci fi cally binding to EhMLBP also impaired the growth of trophozoites (Lavi et al 2008 ) . These data support the view that deciphering the unique features of epigenetic regulation may pinpoint novel targets for antiamebic chemotherapy.…”

Section: Entamoeba Histolytica -Methylated Line-binding Proteinmentioning

confidence: 98%