Calcium Modulates Promoter Occupancy by the Entamoeba histolytica Ca2+-binding Transcription Factor URE3-BP

Gilchrist, Carol A.; Leo, Megan; Line, C. Genghis; Mann, Barbara J.; Petri, William A.

doi:10.1074/jbc.m211271200

Cited by 31 publications

(27 citation statements)

References 38 publications

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“…Intracellular Ca 2ϩ fluxes have been observed in E. histolytica upon contact with fibronectin (6) and increased extracellular Ca 2ϩ concentrations (18). The precise Ca 2ϩ concentration of fluxes induced by these extracellular cues has not been determined.…”

Section: Discussionmentioning

confidence: 99%

“…URE3-BP localized to both the nucleus and the cytoplasm of trophozoites and was also found to be enriched in the plasma membrane. Ca 2ϩ induced the release of binding of URE3-BP from the URE3 motif in vitro and in vivo (18). Mutation of the second EF-hand motif at residues critical for Ca 2ϩ coordination abrogated this effect and allowed for the genome-wide identification of targets of URE3-BP in parasites overexpressing the mutant protein (16).…”

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confidence: 99%

“…In Entamoeba, Ca 2ϩ has been implicated in many aspects of the parasite's pathophysiology, including cell motility (35), adhesion to fibronectin (6), cytolytic activity (36), transcriptional regulation (16)(17)(18), and growth and developmental stage transition (25,26). In eukaryotes, these processes are generally mediated by proteins possessing Ca 2ϩ -binding motifs, such as EF-hands, endonexin folds, and C2 domains, which, in response to changes in intracellular Ca 2ϩ levels, are responsible for the transduction of signaling events, several of which have been identified in Entamoeba (for a review, see reference 4).…”

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Phospholipid-Binding Protein EhC2A Mediates Calcium-Dependent Translocation of Transcription Factor URE3-BP to the Plasma Membrane of Entamoeba histolytica

Moreno

Gilchrist²,

Petri

2010

Eukaryot Cell

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The Entamoeba histolytica upstream regulatory element 3-binding protein (URE3-BP) is a transcription factor that binds DNA in a Ca 2؉ -inhibitable manner. The protein is located in both the nucleus and the cytoplasm but has also been found to be enriched in the plasma membrane of amebic trophozoites. We investigated the reason for the unusual localization of URE3-BP at the amebic plasma membrane. The parasite Entamoeba histolytica is the causative agent of amebiasis, estimated to be the second leading protozoan cause of morbidity and mortality in humans worldwide (2). The molecular mechanisms that regulate the outcome of infection have yet to be elucidated; however, we hypothesize that transcriptional regulation may play an essential role in determining such outcomes.The calcium ion (Ca 2ϩ ) is a universal regulator of many cellular processes in eukaryotic cells, including cell signaling events, gene expression, and cell death. In Entamoeba, Ca 2ϩ has been implicated in many aspects of the parasite's pathophysiology, including cell motility (35), adhesion to fibronectin (6), cytolytic activity (36), transcriptional regulation (16-18), and growth and developmental stage transition (25, 26). In eukaryotes, these processes are generally mediated by proteins possessing Ca 2ϩ -binding motifs, such as EF-hands, endonexin folds, and C2 domains, which, in response to changes in intracellular Ca 2ϩ levels, are responsible for the transduction of signaling events, several of which have been identified in Entamoeba (for a review, see reference 4).The upstream regulatory element 3-binding protein (URE3-BP) is an E. histolytica Ca 2ϩ -regulated transcription factor first identified for its roles in the control of the expression of ferredoxin (fdx1) and the heavy subunit of the galactose/N-acetylgalactosamine (Gal/GalNAc)-inhibitable lectin (hgl5). The protein was isolated by a yeast one-hybrid screen using the cognate URE3 DNA motif (17), though the amino acid sequence of URE3-BP revealed no DNA-binding motifs. The protein did, however, possess two canonical and one noncanonical EF-hand motifs. URE3-BP localized to both the nucleus and the cytoplasm of trophozoites and was also found to be enriched in the plasma membrane. Ca 2ϩ induced the release of binding of URE3-BP from the URE3 motif in vitro and in vivo (18). Mutation of the second EF-hand motif at residues critical for Ca 2ϩ coordination abrogated this effect and allowed for the genome-wide identification of targets of URE3-BP in parasites overexpressing the mutant protein (16).In this study, we explored the reason for the unusual plasma membrane localization of the URE3-BP transcription factor. We discovered a novel URE3-BP binding partner, EhC2A, containing an N-terminal Ca 2ϩ -binding C2 domain and a proline-rich C-terminal region. C2 domains are ϳ120-residue motifs that confer phospholipid-binding activity on the majority of proteins which possess them (reviewed in references 9, 22, and 37). EhC2A coimmunoprecipitated with URE3-BP in a Ca 2ϩ -dependent manner and ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Phospholipid-Binding Protein EhC2A Mediates Calcium-Dependent Translocation of Transcription Factor URE3-BP to the Plasma Membrane of Entamoeba histolytica

Moreno

Gilchrist²,

Petri

2010

Eukaryot Cell

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“…The differences were noticed beyond 670 nucleotides upstream of the translation initiation codon ATG. Sequence conservation of the upstream 670 nucleotides was surprising as most of the amoebic promoters have been found very close to the gene (11). It is likely that either the specific promoters or the controlling elements are beyond 670 nucleotides or that an epigenetic mechanism may be involved in determining the expression status of these genes (6).…”

Section: Discussionmentioning

confidence: 99%

“…Signal transduction pathways involving calcium have also been identified (27,28). These pathways are mediated through a number of calcium binding proteins, including calmodulin (24), a novel calcium binding transcription regulator (11), and a novel protein involved in actin cytoskeletal dynamics (30).…”

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Expression and Function of a Family of Transmembrane Kinases from the Protozoan Parasite Entamoeba histolytica

et al. 2006

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The signaling proteome of Entamoeba histolytica is made of transmembrane kinases (TMKs) that are rarely found in unicellular eukaryotes. There are 90 TMK genes reported for E. histolytica, and these have been grouped into nine distinct families based on motifs present on both extracellular and kinase domains. Of these, the B1 family was chosen for further analysis. Genomic sequencing revealed the presence of 28 members belonging to this family. Genes corresponding to the majority of these were truncated and not considered for further analysis. Only five members were full length and contained both extracellular and cytosolic kinase domains. BLAST analysis revealed the presence of homologs of these B1 TMKs in the nonpathogenic Entamoeba dispar. However, the ligand binding domains of the orthologous B1 TMKs of the two species showed considerable divergence, indicating the possibility of a correlation with the pathogenic potential of the organism. Only two of the five full-length copies (B1.I.1 and B1.I.2) were expressed in E. histolytica under the culture conditions used. Antisera generated against the extracellular domain of B1.I.1 stained the cell surface, particularly the areas of contact between the trophozoites. Staining was also seen in the frontal and posterior regions of the motile amoeba. An amoebic cell line expressing a truncated version of the B1.I.1 that lacked the kinase domain was generated. Inducible expression of the truncated TMK resulted in a decrease in cellular proliferation and an increase in sensitivity to serum starvation. Our data indicate that the B1

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Deciphering molecular mechanisms of mRNA metabolism in the deep‐branching eukaryote Entamoeba histolytica

López-Camarillo¹,

López-Rosas²,

Ospina-Villa

et al. 2013

WIREs RNA

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Although extraordinary rapid advance has been made in the knowledge of mechanisms regulating messenger RNA (mRNA) metabolism in mammals and yeast, little information is known in deep-branching eukaryotes. The complete genome sequence of Entamoeba histolytica, the protozoan parasite responsible for human amoebiasis, provided a lot of information for the identification and comparison of regulatory sequences and proteins potentially involved in mRNA synthesis, processing, and degradation. Here, we review the current knowledge of mRNA metabolism in this human pathogen. Several DNA motifs in promoter and nuclear factors involved in transcription, as well as conserved polyadenylation sequences in mRNA 3'-untranslated region and possible cleavage and polyadenylation factors, are described. In addition, we present recent data about proteins involved in mRNA decay with a special focus on the recently reported P-bodies in amoeba. Models for mechanisms of decapping and deadenylation-dependent pathways are discussed. We also review RNA-based gene silencing mechanisms and describe the DEAD/DExH box RNA helicases that are molecular players in all mRNA metabolism reactions. The functional characterization of selected proteins allows us to define a general framework to describe how mRNA synthesis, processing, and decay may occur in E. histolytica. Taken altogether, studies of mRNA metabolism in this single-celled eukaryotic model suggest the conservation of specific gene expression regulatory events through evolution.

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Calcium Modulates Promoter Occupancy by the Entamoeba histolytica Ca2+-binding Transcription Factor URE3-BP

Cited by 31 publications

References 38 publications

Phospholipid-Binding Protein EhC2A Mediates Calcium-Dependent Translocation of Transcription Factor URE3-BP to the Plasma Membrane of Entamoeba histolytica

Phospholipid-Binding Protein EhC2A Mediates Calcium-Dependent Translocation of Transcription Factor URE3-BP to the Plasma Membrane of Entamoeba histolytica

Expression and Function of a Family of Transmembrane Kinases from the Protozoan Parasite Entamoeba histolytica

Deciphering molecular mechanisms of mRNA metabolism in the deep‐branching eukaryote Entamoeba histolytica

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