TOX4 and its binding partners recognize DNA adducts generated by platinum anticancer drugs

Puch, Christophe Bounaix Morand Du; Barbier, Ewa; Kraut, Alexandra; Couté, Yohann; Fuchs, Julia; Buhot, Arnaud; Livache, Thierry; Sève, Michel; Favier, Alain; Douki, Thierry; Gasparutto, Didier; Sauvaigo, Sylvie; Breton, Jean

doi:10.1016/j.abb.2010.12.021

Cited by 37 publications

(30 citation statements)

References 41 publications

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“…TOX is part of the larger HMG-box superfamily of proteins, but also defines a small subfamily of proteins including TOX2, TOX3 and TOX4, all of which are highly conserved in vertebrate species (Figure 1) [2]. While the in vivo functions of TOX have been best characterized, TOX2 may play a role in reproductive organs [3], TOX3 has been implicated in regulation of neuron cell survival [4] and breast cancer [5,6], and TOX4 is known to interact with a phosphatase complex involved in the control of chromatin structure and cell cycle progression [7,8]. …”

Section: Introductionmentioning

confidence: 99%

The many roles of TOX in the immune system

Aliahmad

Seksenyan

Kaye

2012

Current Opinion in Immunology

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TOX is a member of an evolutionarily conserved DNA-binding protein family and is expressed in several immune-relevant cell subsets. Here, we review the key role of TOX in regulating development of CD4 T cells, natural killer cells and lymphoid tissue inducer cells, the latter responsible for the generation of lymph nodes. Although the exact molecular mechanism of action of TOX remains to be elucidated, the role of TOX in establishment of gene programs in the thymus and the potential of TOX as a regulator of E protein activity are discussed.

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Section: Introductionmentioning

confidence: 99%

The many roles of TOX in the immune system

Aliahmad

Seksenyan

Kaye

2012

Current Opinion in Immunology

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“…Consistent with this function, our data also revealed that epigenetic inactivation of TOX3 specifically modulates pathways involved in synaptogenesis and axonal guidance. A recent study revealed that TOX4 is recruited to DNA-damage specifically induced by platinum compounds (cisplatin and oxaliplatin but not UV) indicating a potential role in DNA damage and repair [24]. Currently, there is no data regarding the normal function of TOX2.…”

Section: Discussionmentioning

confidence: 99%

“…TOX3 is a neuronal survival factor that is highly expressed and regulates calcium dependent transcription in neurons [22], [23]. The expression profile and specific function of TOX4 is yet known, but this protein has been demonstrated to recognize DNA adducts specifically generated by platinum based anticancer drugs, suggesting it might function in DNA damage response and DNA repair pathways [24]. However, in contrast to a growing number of studies demonstrating abnormalities including aberrant promoter CpG island hypermethylation of multiple HMG proteins in various human malignancies, the role of TOX subfamily in carcinogenesis is unclear [25], [26], [27], [28], [29], [30], [31].…”

Section: Introductionmentioning

confidence: 99%

Differential Epigenetic Regulation of TOX Subfamily High Mobility Group Box Genes in Lung and Breast Cancers

et al. 2012

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Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p<0.05). These transcripts were silenced in methylated lung and breast cancer cells and 5-Aza-2-deoxycytidine treatment re-expressed both. Extension of these assays to TOX, TOX3, and TOX4 genes that share similar genomic structure and protein homology with TOX2 revealed distinct methylation profiles by smoking status, histology, and cancer type. TOX was almost exclusively methylated in breast (43%) than lung (5%) cancer, whereas TOX3 was frequently methylated in lung (58%) than breast (30%) tumors. TOX4 was unmethylated in all samples and showed the highest expression in normal lung. Compared to TOX4, expression of TOX, TOX2 and TOX3 in normal lung was 25, 44, and 88% lower, respectively, supporting the premise that reduced promoter activity confers increased susceptibility to methylation during lung carcinogenesis. Genome-wide assays revealed that siRNA-mediated TOX2 knockdown modulated multiple pathways while TOX3 inactivation targeted neuronal development and function. Although these knockdowns did not result in further phenotypic changes of lung cancer cells in vitro, the impact on tissue remodeling, inflammatory response, and cell differentiation pathways suggest a potential role for TOX2 in modulating tumor microenvironment.

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“…This approach identified 38 proteins interacting with DNA adducts that were validated by immunoassays and SPRi (Surface Plasmon Resonance imaging). Identified proteins may improve the understanding of molecular and cellular responses to this particular type of anticancer drugs [106]. …”

Section: Chromatography-based Assaysmentioning

confidence: 99%

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

Moraes¹,

Cardoso²,

Seidl³

et al. 2016

CPD

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Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed.

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TOX4 and its binding partners recognize DNA adducts generated by platinum anticancer drugs

Cited by 37 publications

References 41 publications

The many roles of TOX in the immune system

The many roles of TOX in the immune system

Differential Epigenetic Regulation of TOX Subfamily High Mobility Group Box Genes in Lung and Breast Cancers

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

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