The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ian De Belle - One of the best experts on this subject based on the ideXlab platform.
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TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Sabina Sperandio, Corinne Barat, Miguel A. Cabrita, Ana Gargaun, Maxim V. Berezovski, Michel J. Tremblay, Ian De BelleAbstract:Target of Egr1 (TOE1) is a nuclear protein localized primarily in nucleoli and Cajal bodies that was identified as a downstream target of the immediate early gene Egr1. TOE1 displays a functional deadenylation domain and has been shown to participate in spliceosome assembly. We report here that TOE1 can function as an inhibitor of HIV-1 replication and show evidence that supports a direct interaction of TOE1 with the viral specific transactivator response element as part of the inhibitory mechanism. In addition, we show that TOE1 can be secreted by activated CD8+ T lymphocytes and can be cleaved by the serine protease granzyme B, one of the main components of cytotoxic granules. Both full-length and cleaved TOE1 can spontaneously cross the plasma membrane and penetrate cells in culture, retaining HIV-1 inhibitory activity. Antiviral potency of TOE1 and its cell-penetrating capability have been identified to lie within a 35-amino-acid region containing the nuclear localization sequence.
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TOE1 interacts with p53 to modulate its transactivation potential
FEBS letters, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53.
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Abstract #1529: The Egr1 target TOE1 interacts with p53 to modulate its transactivation
Cancer Research, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1529.
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abstract 1529 the egr1 target TOE1 interacts with p53 to modulate its transactivation
Cancer Research, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1529.
Naiara Akizu - One of the best experts on this subject based on the ideXlab platform.
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Biallelic mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing
Nature Genetics, 2017Co-Authors: Rea M Lardelli, Veerle Rc Eggens, Ashleigh E Schaffer, Maha S Zaki, Stephanie Grainger, Shashank Sathe, Eric L Van Nostrand, Zinayida Schlachetzki, Basak Rosti, Naiara AkizuAbstract:Jens Lykke-Andersen, Frank Baas, Joseph Gleeson and colleagues report that mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia type 7. They further show that these mutations result in the accumulation of incompletely processed small nuclear RNAs, leading to severe, early-onset neurodegeneration. Deadenylases are best known for degrading the poly(A) tail during mRNA decay. The deadenylase family has expanded throughout evolution and, in mammals, consists of 12 Mg^2+-dependent 3′-end RNases with substrate specificity that is mostly unknown^ 1 . Pontocerebellar hypoplasia type 7 (PCH7) is a unique recessive syndrome characterized by neurodegeneration and ambiguous genitalia^ 2 . We studied 12 human families with PCH7, uncovering biallelic, loss-of-function mutations in TOE1 , which encodes an unconventional deadenylase^ 3 , 4 . TOE1 -morphant zebrafish displayed midbrain and hindbrain degeneration, modeling PCH-like structural defects in vivo . Surprisingly, we found that TOE1 associated with small nuclear RNAs (snRNAs) incompletely processed spliceosomal. These pre-snRNAs contained 3′ genome-encoded tails often followed by post-transcriptionally added adenosines. Human cells with reduced levels of TOE1 accumulated 3′-end-extended pre-snRNAs, and the immunoisolated TOE1 complex was sufficient for 3′-end maturation of snRNAs. Our findings identify the cause of a neurodegenerative syndrome linked to snRNA maturation and uncover a key factor involved in the processing of snRNA 3′ ends.
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Biallelic mutations in the 3' exonuclease TOE1 cause pontocerebellar hypoplasia and uncover a role in snRNA processing.
Nature genetics, 2017Co-Authors: Rea M Lardelli, Veerle Rc Eggens, Ashleigh E Schaffer, Maha S Zaki, Stephanie Grainger, Shashank Sathe, Eric L Van Nostrand, Zinayida Schlachetzki, Basak Rosti, Naiara AkizuAbstract:Jens Lykke-Andersen, Frank Baas, Joseph Gleeson and colleagues report that mutations in the 3′ exonuclease TOE1 cause pontocerebellar hypoplasia type 7. They further show that these mutations result in the accumulation of incompletely processed small nuclear RNAs, leading to severe, early-onset neurodegeneration.
Sabina Sperandio - One of the best experts on this subject based on the ideXlab platform.
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TOE1 is an inhibitor of HIV-1 replication with cell-penetrating capability
Proceedings of the National Academy of Sciences of the United States of America, 2015Co-Authors: Sabina Sperandio, Corinne Barat, Miguel A. Cabrita, Ana Gargaun, Maxim V. Berezovski, Michel J. Tremblay, Ian De BelleAbstract:Target of Egr1 (TOE1) is a nuclear protein localized primarily in nucleoli and Cajal bodies that was identified as a downstream target of the immediate early gene Egr1. TOE1 displays a functional deadenylation domain and has been shown to participate in spliceosome assembly. We report here that TOE1 can function as an inhibitor of HIV-1 replication and show evidence that supports a direct interaction of TOE1 with the viral specific transactivator response element as part of the inhibitory mechanism. In addition, we show that TOE1 can be secreted by activated CD8+ T lymphocytes and can be cleaved by the serine protease granzyme B, one of the main components of cytotoxic granules. Both full-length and cleaved TOE1 can spontaneously cross the plasma membrane and penetrate cells in culture, retaining HIV-1 inhibitory activity. Antiviral potency of TOE1 and its cell-penetrating capability have been identified to lie within a 35-amino-acid region containing the nuclear localization sequence.
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TOE1 interacts with p53 to modulate its transactivation potential
FEBS letters, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53.
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Abstract #1529: The Egr1 target TOE1 interacts with p53 to modulate its transactivation
Cancer Research, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1529.
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abstract 1529 the egr1 target TOE1 interacts with p53 to modulate its transactivation
Cancer Research, 2009Co-Authors: Sabina Sperandio, Saverio Tardito, Aleksandra Surzycki, Martin Latterich, Ian De BelleAbstract:The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1529.
Shuangfeng Wang - One of the best experts on this subject based on the ideXlab platform.
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mir172b TOE1 2 module regulates plant innate immunity in an age dependent manner
Biochemical and Biophysical Research Communications, 2020Co-Authors: Yanmin Zou, Shuangfeng WangAbstract:Plant innate immunity varies with age and plant developmental stages. Recently, we reported that Arabidopsis thaliana microRNA miR172b regulates FLS2 transcription through two transcription factors: TARGET OF EAT1 (TOE1) and TOE2. Although the flg22-triggered immune responses were investigated in 2-d-old or even younger TOE1/toe2 mutant and miR172b over expression (OE) transgenic plants, the FLS2-mediated immune responses in older plants remain uncharacterized yet. In this work, we analyzed the flg22-triggered immune response in 6-d-old TOE1/toe2 and miR172b OE plants. We found that unlike 2-d-old plants, 6-d-old Col-0, TOE1/toe2 and miR172b OE plants exhibit comparable flg22-triggered immune responses. Strikingly, miR172b precursor in 6-d-old Col-0 plants upon flg22 treatment reached to a very high level, consequently, the TOE1/2 protein level under this condition was very low or almost undetectable, which explains why 6-d-old WT seedlings are very similar to TOE1/toe2 seedlings or miR172b OE plants with respect to the flg22-triggered immune responses. Taken together, our study reveals that miR172b-TOE1/2 module regulates plant innate immunity in an age-dependent manner.
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MiR172b-TOE1/2 module regulates plant innate immunity in an age-dependent manner.
Biochemical and biophysical research communications, 2020Co-Authors: Yanmin Zou, Shuangfeng WangAbstract:Plant innate immunity varies with age and plant developmental stages. Recently, we reported that Arabidopsis thaliana microRNA miR172b regulates FLS2 transcription through two transcription factors: TARGET OF EAT1 (TOE1) and TOE2. Although the flg22-triggered immune responses were investigated in 2-d-old or even younger TOE1/toe2 mutant and miR172b over expression (OE) transgenic plants, the FLS2-mediated immune responses in older plants remain uncharacterized yet. In this work, we analyzed the flg22-triggered immune response in 6-d-old TOE1/toe2 and miR172b OE plants. We found that unlike 2-d-old plants, 6-d-old Col-0, TOE1/toe2 and miR172b OE plants exhibit comparable flg22-triggered immune responses. Strikingly, miR172b precursor in 6-d-old Col-0 plants upon flg22 treatment reached to a very high level, consequently, the TOE1/2 protein level under this condition was very low or almost undetectable, which explains why 6-d-old WT seedlings are very similar to TOE1/toe2 seedlings or miR172b OE plants with respect to the flg22-triggered immune responses. Taken together, our study reveals that miR172b-TOE1/2 module regulates plant innate immunity in an age-dependent manner.
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Transcriptional Regulation of the Immune Receptor FLS2 Controls the Ontogeny of Plant Innate Immunity
The Plant cell, 2018Co-Authors: Yanmin Zou, Shuangfeng Wang, Yuanyuan Zhou, Jiaojiao Bai, Guozhong Huang, Liu Xiaotong, Yingying Zhang, Dingzhong TangAbstract:Innate immunity plays a vital role in protecting plants and animals from pathogen infections. Immunity varies with age in both animals and plants. However, little is known about the ontogeny of plant innate immunity during seedling development. We report here that the Arabidopsis (Arabidopsis thaliana) microRNA miR172b regulates the transcription of the immune receptor gene FLAGELLIN-SENSING2 (FLS2) through TARGET OF EAT1 (TOE1) and TOE2, which directly bind to the FLS2 promoter and inhibit its activity. The level of miR172b is very low in the early stage of seedling development but increases over time, which results in decreased TOE1/2 protein accumulation and, consequently, increased FLS2 transcription and the ontogeny of FLS2-mediated immunity during seedling development. Our study reveals a role for the miR172b-TOE1/2 module in regulating plant innate immunity and elucidates a regulatory mechanism underlying the ontogeny of plant innate immunity.plantcell;30/11/2779/FX1F1fx1.
Janice De Almeida-engler - One of the best experts on this subject based on the ideXlab platform.
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A role for the gene regulatory module microRNA172/TARGET OF EARLY ACTIVATION TAGGED 1/FLOWERING LOCUS T (miRNA172/TOE1/FT) in the feeding sites induced by Meloidogyne javanica in Arabidopsis thaliana
New Phytologist, 2018Co-Authors: Fernando E. Diaz-manzano, Javier Cabrera, Juan Jose Ripoll, Mari Fe Andres, Ana Claudia Silva, Marta Barcala, Ivan Del Olmo, Maria Sanchez, Virginia Ruiz-ferrer, Janice De Almeida-englerAbstract:Root knot nematodes (RKNs) penetrate into the root vascular cylinder, triggering morphogenetic changes to induce galls, de novo formed 'pseudo-organs' containing several giant cells (GCs). Distinctive gene repression events observed in early gall/GCs development are thought to be mediated by post-transcriptional silencing via microRNAs (miRNAs), a process that is far from being fully characterized. Arabidopsis thaliana backgrounds with altered activities based on target 35S::MIMICRY172 (MIM172), 35S::TARGET OF EARLY ACTIVATION TAGGED 1 (TOE1)-miR172-resistant (35S::TOE1(R)) and mutant (flowering locus T-10 (ft-10)) lines were used for functional analysis of nematode infective and reproductive parameters. The GUS-reporter lines, MIR172A-E::GUS, treated with auxin (IAA) and an auxin-inhibitor (a-(phenyl ethyl-2-one)-indole-3-acetic acid (PEO-IAA)), together with the MIR172C AuxRE::GUS line with two mutated auxin responsive elements (AuxREs), were assayed for nematode-dependent gene expression. Arabidopsis thaliana backgrounds with altered expression of miRNA172, TOE1 or FT showed lower susceptibility to the RKNs and smaller galls and GCs. MIR172C-D::GUS showed restricted promoter activity in galls/GCs that was regulated by auxins through auxin-responsive factors. IAA induced their activity in galls while PEO-IAA treatment and mutations in AuxRe motifs abolished it. The results showed that the regulatory module miRNA172/TOE1/FT plays an important role in correct GCs and gall development, where miRNA172 is modulated by auxins.