An in vitro characterisation of the Trichomonas vaginalis TATA box-binding proteins (TBPs)

Parra-Marín, Olivia; Rosas-Hernández, Lluvia; López-Pacheco, Karla; Franco, Bernardo; Ibáñez‐Escribano, Alexandra; Hernández, Roberto; López‐Villaseñor, Imelda

doi:10.1007/s00436-019-06438-z

Cited by 6 publications

(4 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, TBPs with sufficient sequence divergence are susceptible to being used as a therapeutic target. An example of this is the TBP of T. vaginalis , which exhibits such divergence that it is not functional in other organisms like S. cerevisiae , as determined through complementation assays [ 43 ]. Our analysis reveals that the NC2 motif of the TBP in the parasite studied here is highly divergent in sequence, as no amino acid residue is conserved in Gl TBP compared to the Hs TBP ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents

Gaona-López,

Méndez-Álvarez,

Moreno-Rodríguez

et al. 2024

IJMS

View full text Add to dashboard Cite

Parasitic diseases, predominantly prevalent in developing countries, are increasingly spreading to high-income nations due to shifting migration patterns. The World Health Organization (WHO) estimates approximately 300 million annual cases of giardiasis. The emergence of drug resistance and associated side effects necessitates urgent research to address this growing health concern. In this study, we evaluated over eleven thousand pharmacological compounds sourced from the FDA database to assess their impact on the TATA-binding protein (TBP) of the early diverging protist Giardia lamblia, which holds medical significance. We identified a selection of potential pharmacological compounds for combating this parasitic disease through in silico analysis, employing molecular modeling techniques such as homology modeling, molecular docking, and molecular dynamics simulations. Notably, our findings highlight compounds DB07352 and DB08399 as promising candidates for inhibiting the TBP of Giardia lamblia. Also, these compounds and DB15584 demonstrated high efficacy against trophozoites in vitro. In summary, this study identifies compounds with the potential to combat giardiasis, offering the prospect of specific therapies and providing a robust foundation for future research.

show abstract

Section: Discussionmentioning

confidence: 99%

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents

Gaona-López,

Méndez-Álvarez,

Moreno-Rodríguez

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…IBP39 does not display homology to any other transcription factor in the database and is exclusive of the Trichomonas genus. Furthermore, two TBPs have been identified, one of which binds to T. vaginalis gene promoter regions, and the other (TvTBP1) interacts with IBP39, suggesting that they might be part of a PIC at RNAPII core promoters [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Initiator-Directed Transcription: Fission Yeast Nmtl Initiator Directs Preinitiation Complex Formation and Transcriptional Initiation

Rojas

Urbina

Valenzuela-Pérez

et al. 2022

Genes

View full text Add to dashboard Cite

The initiator element is a core promoter element encompassing the transcription start site, which is found in yeast, Drosophila, and human promoters. This element is observed in TATA-less promoters. Several studies have defined transcription factor requirements and additional cofactors that are needed for transcription initiation of initiator-containing promoters. However, those studies have been performed with additional core promoters in addition to the initiator. In this work, we have defined the pathway of preinitiation complex formation on the fission yeast nmt1 gene promoter, which contains a functional initiator with striking similarity to the initiator of the human dihydrofolate reductase (hDHFR) gene and to the factor requirement for transcription initiation of the nmt1 gene promoter. The results show that the nmt1 gene promoter possesses an initiator encompassing the transcription start site, and several conserved base positions are required for initiator function. A preinitiation complex formation on the nmt1 initiator can be started by TBP/TFIIA or TBP/TFIIB, but not TBP alone, and afterwards follows the same pathway as preinitiation complex formation on TATA-containing promoters. Transcription initiation is dependent on the general transcription factors TBP, TFIIB, TFIIE, TFIIF, TFIIH, RNA polymerase II, Mediator, and a cofactor identified as transcription cofactor for initiator function (TCIF), which is a high-molecular-weight protein complex of around 500 kDa. However, the TAF subunits of TFIID were not required for the nmt1 initiator transcription, as far as we tested. We also demonstrate that other initiators of the nmt1/hDHFR family can be transcribed in fission yeast whole-cell extracts.

show abstract

“…Another extensively studied metazoan core promoter element is the TATA box (Gross & Oelgeschlager, 2006). Although only few T. vaginalis genes have been shown to contain TATA‐like motif in their promoter regions (Noel et al., 2010; Simoes‐Barbosa et al., 2008), two putative TATA box binding proteins (TvTBP1 and TvTBP2) have been recently identified (Parra‐Marin et al., 2019). However, in this work, the authors demonstrated that both proteins are expressed under normal growing conditions and interact with DNA in a non‐specific manner (Parra‐Marin et al., 2019), suggesting a promiscuous role in the transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

“…Although only few T. vaginalis genes have been shown to contain TATA‐like motif in their promoter regions (Noel et al., 2010; Simoes‐Barbosa et al., 2008), two putative TATA box binding proteins (TvTBP1 and TvTBP2) have been recently identified (Parra‐Marin et al., 2019). However, in this work, the authors demonstrated that both proteins are expressed under normal growing conditions and interact with DNA in a non‐specific manner (Parra‐Marin et al., 2019), suggesting a promiscuous role in the transcriptional regulation. Alternatively, two novel eukaryotic core promoter elements, called motif 3 (M3) and motif 5 (M5), have also been found in T. vaginalis (Smith & Johnson, 2011).…”

Section: Introductionmentioning

confidence: 99%

Toward incorporating epigenetics into regulation of gene expression in the parasite Trichomonasvaginalis

Lizarraga

Muñoz

Strobl-Mazzulla

et al. 2021

Molecular Microbiology

View full text Add to dashboard Cite

Trichomonas vaginalis is an extracellular parasite that colonizes the human urogenital tract, causing a highly prevalent sexually transmitted infection. The parasite must change its transcriptional profile in order to establish and maintain infection. However, few core regulatory elements and transcription factors have been identified to date and little is known about other mechanisms that may control these rapid changes in gene expression during parasite infection. In the last years, epigenetic mechanisms involved in the regulation of gene expression have been gaining major attention in this parasite. In this review, we summarize and discuss the major advances of the last few years with regard to epigenetics (DNA methylation, post‐translational histone modifications, and histone variants) in the parasite T. vaginalis. These studies can shed light into our current understanding of this parasite's biology with far‐reaching implications for the prognosis and treatment of trichomoniasis.

show abstract

An in vitro characterisation of the Trichomonas vaginalis TATA box-binding proteins (TBPs)

Cited by 6 publications

References 55 publications

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents

TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents

Initiator-Directed Transcription: Fission Yeast Nmtl Initiator Directs Preinitiation Complex Formation and Transcriptional Initiation

Toward incorporating epigenetics into regulation of gene expression in the parasite Trichomonasvaginalis

Contact Info

Product

Resources

About