Endocrine disrupting chemicals may deregulate DNA repair through estrogen receptor mediated seizing of CBP/p300 acetylase

Lakshmanan, M.; Shaheer, Koniyan

doi:10.1007/s40618-020-01241-5

Cited by 18 publications

(8 citation statements)

References 73 publications

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“…After activated by estrogen, the complex of estrogen and ER transfers to nuclear and locates to the estrogen response elements (ERE) in the distal enhancer regions of target genes [ 18 ]. Together with the coordinate regulators (p300/CBP, c-Jun, GATA3 and FOXA1), the activated ER enhancer regulates the genomic remodeling, including open chromatin architecture, histone modifications and trigger the ER-dependent genes transcription [ 19 , 20 ]. On the other hand, the ER enhancer is able to connect with RNA polymerase II and promotes a series of noncoding enhancer RNAs transcription, called enhancer RNA (eRNA) [ 21 ].…”

Section: Estrogen and Estrogen Receptormentioning

confidence: 99%

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

Wang¹,

Jin

Qian

et al. 2021

Cancer Cell Int

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As the essential sexual hormone, estrogen and its receptor has been proved to participate in the regulation of autoimmunity diseases and anti-tumor immunity. The adjustment of tumor immunity is related to the interaction between cancer cells, immune cells and tumor microenvironment, all of which is considered as the potential target in estrogen-induced immune system regulation. However, the specific mechanism of estrogen-induced immunity is poorly understood. Typically, estrogen causes the nuclear localization of estrogen/estrogen receptor complex and alternates the transcription pattern of target genes, leading to the reprogramming of tumor cells and differentiation of immune cells. However, the estrogen-induced non-canonical signal pathway activation is also crucial to the rapid function of estrogen, such as NF-κB, MAPK-ERK, and β-catenin pathway activation, which has not been totally illuminated. So, the investigation of estrogen modulatory mechanisms in these two manners is vital for the tumor immunity and can provide the potential for endocrine hormone targeted cancer immunotherapy. Here, this review summarized the estrogen-induced canonical and non-canonical signal transduction pathway and aimed to focus on the relationship among estrogen and cancer immunity as well as immune-related tumor microenvironment regulation. Results from these preclinical researches elucidated that the estrogen-target therapy has the application prospect of cancer immunotherapy, which requires the further translational research of these treatment strategies.

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Section: Estrogen and Estrogen Receptormentioning

confidence: 99%

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

Wang¹,

Jin

Qian

et al. 2021

Cancer Cell Int

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“…Mechanistically, EDCs may behave similarly to the endogenous hormones that they mimic and bind to or interfere with the binding of endogenous hormone receptors (e.g., steroid receptors) or other binding proteins involved in hormone physiology and action, ultimately impacting receptor chromatin modification and transcriptional functions (Lakshmanan & Shaheer, 2020 ; Martini et al, 2020 ). Directly, by binding to hormone receptors, or indirectly, by changing recruitment patterns of TFs, including Ctcf, EDCs could reprogram the germline at different stages of development (Fiorito et al, 2016 ).…”

Section: Evidence Of Germ Cell Alterations Caused By Exogenous Factor...mentioning

confidence: 99%

Beyond Genes: Germline Disruption in the Etiology of Autism Spectrum Disorders

Escher¹,

Yan

Rissman

et al. 2021

J Autism Dev Disord

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Investigations into the etiology of autism spectrum disorders have been largely confined to two realms: variations in DNA sequence and somatic developmental exposures. Here we suggest a third route—disruption of the germline epigenome induced by exogenous toxicants during a parent’s gamete development. Similar to cases of germline mutation, these molecular perturbations may produce dysregulated transcription of brain-related genes during fetal and early development, resulting in abnormal neurobehavioral phenotypes in offspring. Many types of exposures may have these impacts, and here we discuss examples of anesthetic gases, tobacco components, synthetic steroids, and valproic acid. Alterations in parental germline could help explain some unsolved phenomena of autism, including increased prevalence, missing heritability, skewed sex ratio, and heterogeneity of neurobiology and behavior.

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“…All the known NRs discovered so far adopts common structural and functional characteristics and consists of evolutionarily conserved, structurally and functionally distinct three to six basic domains (Lakshmanan and Shaheer, 2020). ERs are made up of an N-terminal domain, central DNA binding domain, C-terminal LBD, and two distinct, conformationally active regions designated as activation function 1 (AF-1) and activation function 2 (AF-2) (Lakshmanan and Sadasivan, 2014).…”

Section: Lbd Of Estrogen Hormone Receptors Are Specific Toward Its Endogenous Ligandmentioning

confidence: 99%

“…DNA-binding domain (DBD) is the most conserved among the domains, and the N-terminal domain is most variable in sequence and length. ER signaling depends on the ligand/hormone and begins with the binding of ligand to LBD (Lakshmanan and Shaheer, 2020). LBDs of nuclear hormones are specific toward its endogenous ligand and normally do not cross-interact with other non-specific endogenous hormones (Sasson and Notides, 1983;Klinge, 2001;Razandi et al, 2004;Yang et al, 2004;Morissette et al, 2008).…”

Section: Lbd Of Estrogen Hormone Receptors Are Specific Toward Its Endogenous Ligandmentioning

confidence: 99%

“…Estrogen hormone receptors exhibits least substrate specificity and strong binding affinities for most of the steroid/phenolic and few of the non-phenolic/non-steroid agents classified as xenoestrogens (Cauley, 2015;Gore et al, 2015;Shafei et al, 2018;Pacyga et al, 2019;Rosenfeld and Cooke, 2019;Basak et al, 2020;Lakshmanan and Shaheer, 2020;Park et al, 2020). It is interesting to explore why a receptor that shows high specificity to its endogenous ligand can be transactivated by other hormone metabolites or chemically distinct exogenous agents.…”

Section: Why Ers Are Responsive To An Array Of Diverse Exogenous Substances?mentioning

confidence: 99%

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Ligand Binding Domain of Estrogen Receptor Alpha Preserve a Conserved Structural Architecture Similar to Bacterial Taxis Receptors

Mangalath

Mohammed

2021

Front. Ecol. Evol.

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It remains a mystery why estrogen hormone receptors (ERs), which are highly specific toward its endogenous hormones, are responsive to chemically distinct exogenous agents. Does it indicate that ERs are environmentally regulated? Here, we speculate that ERs would have some common structural features with prokaryotic taxis receptor responsive toward environmental signals. This study addresses the low specificity and high responsiveness of ERs toward chemically distinct exogenous substances, from an evolutionary point of view. Here, we compared the ligand binding domain (LBD) of ER alpha (α) with the LBDs of prokaryotic taxis receptors to check if LBDs share any structural similarity. Interestingly, a high degree of similarity in the domain structural fold architecture of ERα and bacterial taxis receptors was observed. The pharmacophore modeling focused on ligand molecules of both receptors suggest that these ligands share common pharmacophore features. The molecular docking studies suggest that the natural ligands of bacterial chemotaxis receptors exhibit strong interaction with human ER as well. Although phylogenetic analysis proved that these proteins are unrelated, they would have evolved independently, suggesting a possibility of convergent molecular evolution. Nevertheless, a remarkable sequence divergence was seen between these proteins even when they shared common domain structural folds and common ligand-based pharmacophore features, suggesting that the protein architecture remains conserved within the structure for a specific function irrespective of sequence identity.

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Endocrine disrupting chemicals may deregulate DNA repair through estrogen receptor mediated seizing of CBP/p300 acetylase

Cited by 18 publications

References 73 publications

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

Estrogen/ER in anti-tumor immunity regulation to tumor cell and tumor microenvironment

Beyond Genes: Germline Disruption in the Etiology of Autism Spectrum Disorders

Ligand Binding Domain of Estrogen Receptor Alpha Preserve a Conserved Structural Architecture Similar to Bacterial Taxis Receptors

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