<i>Trichomonas vaginalis</i>Cysteine Proteinases: Iron Response in Gene Expression and Proteolytic Activity

Arroyo, Rossana; Cárdenas-Guerra, Rosa Elena; Figueroa-Angulo, Elisa E.; Puente-Rivera, Jonathan; Zamudio-Prieto, Olga; Ortega‐López, Jaime

doi:10.1155/2015/946787

Cited by 35 publications

(54 citation statements)

References 111 publications

(322 reference statements)

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“…Although some cysteine proteases are reportedly regulated at the posttranscriptional level by an iron-responsive element/iron response protein-like system56, iron-dependent gene regulation at the transcriptional level has been described only for the ap65 - 1 gene. The ap65 - 1 gene has an iron-inducible core promoter and several regulatory elements that are recognized by three Myb transcription factors, TvMyb1, TvMyb2, and TvMyb3303132333435.…”

Section: Discussionmentioning

confidence: 99%

“…The ap65 - 1 gene has an iron-inducible core promoter and several regulatory elements that are recognized by three Myb transcription factors, TvMyb1, TvMyb2, and TvMyb3303132333435. Although the presence of Myb recognition elements are shared by other genes, no direct evidence on the role of this regulatory element in iron-dependent gene transcription has been provided for other genes56. In the present study, we reported for the first time that histone modifications contribute to iron-dependent transcriptional regulation in T. vaginalis .…”

Section: Discussionmentioning

confidence: 99%

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Epigenome mapping highlights chromatin-mediated gene regulation in the protozoan parasite Trichomonas vaginalis

Song

Choi

et al. 2017

Sci Rep

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Trichomonas vaginalis is an extracellular flagellated protozoan parasite that causes trichomoniasis, one of the most common non-viral sexually transmitted diseases. To survive and to maintain infection, T. vaginalis adapts to a hostile host environment by regulating gene expression. However, the mechanisms of transcriptional regulation are poorly understood for this parasite. Histone modification has a marked effect on chromatin structure and directs the recruitment of transcriptional machinery, thereby regulating essential cellular processes. In this study, we aimed to outline modes of chromatin-mediated gene regulation in T. vaginalis. Inhibition of histone deacetylase (HDAC) alters global transcriptional responses and induces hyperacetylation of histones and hypermethylation of H3K4. Analysis of the genome of T. vaginalis revealed that a number of enzymes regulate histone modification, suggesting that epigenetic mechanisms are important to controlling gene expression in this organism. Additionally, we describe the genome-wide localization of two histone H3 modifications (H3K4me3 and H3K27Ac), which we found to be positively associated with active gene expression in both steady and dynamic transcriptional states. These results provide the first direct evidence that histone modifications play an essential role in transcriptional regulation of T. vaginalis, and may help guide future epigenetic research into therapeutic intervention strategies against this parasite.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epigenome mapping highlights chromatin-mediated gene regulation in the protozoan parasite Trichomonas vaginalis

Song

Choi

et al. 2017

Sci Rep

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“…More recent quantitative proteomic analyses have identified surface membrane proteins that are released to the T. vaginalis environment upon cleavage by rhomboid protease (31). The best-studied group of secreted proteins is the proteases, including cysteine proteases and metalloproteases (17,32,33). Kucknoor et al (34) identified 32 various secreted proteins, including a putative adhesin, AP65, via 2-D SDS-PAGE followed by MALDI-TOF (34).…”

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confidence: 99%

Dynamic secretome of Trichomonas vaginalis: Case study of β-amylases

Štáfková¹,

Rada²,

Meloni³

et al. 2018

Molecular & Cellular Proteomics

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The secretion of virulence factors by parasitic protists into the host environment plays a fundamental role in multifactorial host-parasite interactions. Several effector proteins are known to be secreted by , a human parasite of the urogenital tract. However, a comprehensive profiling of the secretome remains elusive, as do the mechanisms of protein secretion. In this study, we used high-resolution label-free quantitative MS to analyze the secretome, considering that secretion is a time- and temperature-dependent process, to define the cutoff for secreted proteins. In total, we identified 2 072 extracellular proteins, 89 of which displayed significant quantitative increases over time at 37 °C. These 89 secreted proteins were sorted into 13 functional categories. Approximately half of the secreted proteins were predicted to possess transmembrane helixes. These proteins mainly include putative adhesins and leishmaniolysin-like metallopeptidases. The other half of the soluble proteins include several novel potential virulence factors, such as DNaseII, pore-forming proteins, and β-amylases. Interestingly, current bioinformatic tools predicted the secretory signal in only 18% of the identified -secreted proteins. Therefore, we used β-amylases as a model to investigate the secretory pathway. We demonstrated that two β-amylases (BA1 and BA2) are transported via the classical endoplasmic reticulum-to-Golgi pathways, and in the case of BA1, we showed that the protein is glycosylated with multiple -linked glycans of HexHexNAc structure. The secretion was inhibited by brefeldin A but not by FLI-06. Another two β-amylases (BA3 and BA4), which are encoded in the genome but absent from the secretome, were targeted to the lysosomal compartment. Collectively, under defined conditions, our analysis provides a comprehensive set of constitutively secreted proteins that can serve as a reference for future comparative studies, and it provides the first information about the classical secretory pathway in this parasite.

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“…T. vaginalis uses multiple sources of iron from the host cells such as lactoferrin (Lf), hemoglobin (Hb) and heme. It has multiples iron uptake systems mediated by specific receptors: receptor for binding the cytochrome C, a 136 kDa receptor for binding the host holo-Lf and even uses the adhesins AP65 and AP51 as heme- and hemoglobin-binding proteins [ 17 ]. This parasite also internalizes ferritin, but not transferrin.…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins

et al. 2015

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Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis.

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Trichomonas vaginalisCysteine Proteinases: Iron Response in Gene Expression and Proteolytic Activity

Cited by 35 publications

References 111 publications

Epigenome mapping highlights chromatin-mediated gene regulation in the protozoan parasite Trichomonas vaginalis

Epigenome mapping highlights chromatin-mediated gene regulation in the protozoan parasite Trichomonas vaginalis

Dynamic secretome of Trichomonas vaginalis: Case study of β-amylases

RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins

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