Organization of chromatin in cancer cells: role of signalling pathways

1999 ◽  
Vol 77 (4) ◽  
pp. 265-275 ◽  
Author(s):  
J R Davie ◽  
S K Samuel ◽  
V A Spencer ◽  
L T Holth ◽  
D N Chadee ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Nuclear Matrix ◽  
Nuclear Dna ◽  
Mapk Pathway ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Chemical Signalling

The role of mechanical and chemical signalling pathways in the organization and function of chromatin is the subject of this review. The mechanical signalling pathway consists of the tissue matrix system that links together the three-dimensional skeletal networks, the extracellular matrix, cytoskeleton, and nuclear matrix. Intermediate filament proteins are associated with nuclear DNA, suggesting that intermediate filaments may have a role in the organization of chromatin. In human hormone-dependent breast cancer cells, the interaction between cytokeratins and chromatin is regulated by estrogens. Transcription factors, histone acetyltransferases, and histone deacetylases, which are associated with the nuclear matrix, are components of the mechanical signalling pathway. Recently, we reported that nuclear matrix-bound human and chicken histone deacetylase 1 is associated with nuclear DNA in situ, suggesting that histone deacetylase has a role in the organization of nuclear DNA. Chemical signalling pathways such as the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway stimulate the activity of kinases that modify transcription factors, nonhistone chromosomal proteins, and histones. The levels of phosphorylated histones are increased in mouse fibroblasts transformed with oncogenes, the products of which stimulate the Ras/MAPK pathway. Histone phosphorylation may lead to decondensation of chromatin, resulting in aberrant gene expression.Key words: histone acetylation, histone phosphorylation, nuclear matrix, cytoskeleton, histone deacetylase, cancer.

scholarly journals Thymic Regulatory T Cell Development: Role of Signalling Pathways and Transcription Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Mark Engel ◽  
Tom Sidwell ◽  
Ajithkumar Vasanthakumar ◽  
George Grigoriadis ◽  
Ashish Banerjee
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Regulatory T Cells ◽  
Immune Tolerance ◽  
Regulatory T Cell ◽  
T Cell Development ◽  
Signalling Pathways ◽  
Treg Development

Regulatory T cells (Tregs) are a subset of CD4 T cells that are key mediators of immune tolerance. Most Tregs develop in the thymus. In this review we summarise recent findings on the role of diverse signalling pathways and downstream transcription factors in thymic Treg development.

scholarly journals How cancer cells remodel lipid metabolism: strategies targeting transcription factors

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Do-Won Jeong ◽  
Seulbee Lee ◽  
Yang-Sook Chun
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Factors Associated ◽  
Modeling Techniques ◽  
Related Enzyme ◽  
Potential Strategy

AbstractReprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.

scholarly journals The role of vitamin D3 in signaling pathways – potential anticancer properties of calcitriol and its analogues

2019 ◽  
Vol 73 ◽  
pp. 920-936
Author(s):  
Olga Wiecheć
Keyword(s):  
Vitamin D ◽  
Cancer Cells ◽  
Vitamin D3 ◽  
Active Form ◽  
Signalling Pathways ◽  
Active Metabolites ◽  
Anticancer Properties ◽  
Anti Cancer ◽  
Worse Prognosis

Vitamin D, for many years after the discovery, primarily was associated with bone metabolic processes. Currently, many studies indicate its beneficial effect in the prevention and treatment of many diseases, including cancer. However, deficiency of vitamin D is associated with greater tendency to get sick and worse prognosis in treatment, especially cancer. Calcitriol, an active form of vitamin D (1.25(OH)2D3) and its analogues have a pleiotropic activity, including anti-cancer properties. Many studies indicate, that the active forms of vitamin D3 may show anti-proliferative effects in cancer cells by inhibiting the cell cycle, inducing differentiation or leading to apoptosis and enhancing autophagy. Also, extremely important are the possibilities of reducing the invasiveness of tumours through the influence on angiogenesis or adhesion and others. Especially, the anti-cancer role of vitamin D3 is suggested in the case of tumors whose cells express VDR receptors. Interestingly, many cancer cells not only express the VDR receptors, but also due to the expression of CYP27B1 and CYP24A hydroxylases, they can regulate metabolism of calcitriol. Many of the studies using vitamin D3 show that calcitriol and its analogues, due to the influence on cancer cells, can play promising roles in anticancer therapies. Consider the broad pleiotropism of the action of active metabolites of vitamin D3 and the development of research in this field, the current work presents the effect of active forms of vitamin D on some signalling pathways and the regulation of selected proteins in various cancers.

scholarly journals Exosomal MicroRNA-151a-3p Improves the Sensitivity to Radiotherapy via the Interaction between p53 and Histone Deacetylase 5

2021 ◽  
Author(s):  
Seung Min Lee ◽  
Bo Hyun yoon ◽  
Myoung-Hee Kang ◽  
Dong Ha Kim ◽  
Yong-Hee cho ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Cancer Cells ◽  
Histone Deacetylase ◽  
Tumor Suppression ◽  
Bioinformatics Analysis ◽  
Radiation Treatment ◽  
Radiation Equipment ◽  
Exosomal Mirna ◽  
Exosomal Microrna

Abstract Background: Tumor-derived exosomal microRNAs are key elements of the cell-cell communications response to lots of stimuli. However, various functions of the exosome in tumor suppression by radiotherapy (RT) are not clearly understood. Our study showed a previously unknown interaction of p53 and histone deacetylase 5 (HDAC5) by radiation exposure in hepatocellular carcinoma (HCC). Methods: Using serial ultracentrifugation methods, radiation and non-radiation exosomes were purified to investigate the radioresistance of miRNA151a-3p. Radiation doses were treated in 2gy and 4gy using radiation equipment X-RAD 320 to observe the expression of HDAC5 and p53 in hepatic cancer cells. Exosomal miRNA bioinformatics analysis was conducted to find a variation in the miRNA configuration inside Exosome after radiation exposure.Results: HDAC5 and p53 interacted by exposure to radiation, which increased exosome release and altered microRNAs' composition within exosomes. Also, we have described the intercommunication occurring between irradiated and untreated cells via exosomal microRNAs that affect tumor proliferation. In particular, the expression of exosomal microR151a-3p was markedly reduced by radiation treatment. We confirmed that inhibition of exosomal microR151a-3p promotes suppression of non-irradiated cancer cells, thereby increasing RT sensitivity. Conclusion: our present findings demonstrated HDAC5 is a key component of the p53-mediated release of exosomes resulting in tumor suppression through exosomal microRNA-151a-3p in response to radiation. Finally, we highlight the important role of exosomal microRNA 151a-3p as a biomarker in enhancing RT sensitivity.

scholarly journals Evolution of master sex determiners: TGF-β signalling pathways at regulatory crossroads

2021 ◽  
Vol 376 (1832) ◽  
pp. 20200091 ◽  
Author(s):  
Qiaowei Pan ◽  
Tomas Kay ◽  
Alexandra Depincé ◽  
Mateus Adolfi ◽  
Manfred Schartl ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Sex Chromosomes ◽  
Regulatory Network ◽  
Chromosome Evolution ◽  
Sex Chromosome ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Sex Chromosome Evolution ◽  
Theme Issue ◽  
Gene Regulatory

To date, more than 20 different vertebrate master sex-determining genes have been identified on different sex chromosomes of mammals, birds, frogs and fish. Interestingly, six of these genes are transcription factors ( Dmrt1 - or Sox3 - related) and 13 others belong to the TGF-β signalling pathway ( Amh , Amhr2 , Bmpr1b , Gsdf and Gdf6 ). This pattern suggests that only a limited group of factors/signalling pathways are prone to become top regulators again and again. Although being clearly a subordinate member of the sex-regulatory network in mammals, the TGF-β signalling pathway made it to the top recurrently and independently. Facing this rolling wave of TGF-β signalling pathways, this review will decipher how the TGF-β signalling pathways cope with the canonical sex gene regulatory network and challenge the current evolutionary concepts accounting for the diversity of sex-determining mechanisms. This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.

scholarly journals 2-hydroxyglutarate inhibits MyoD-mediated differentiation by preventing H3K9 demethylation

2019 ◽  
Vol 116 (26) ◽  
pp. 12851-12856 ◽  
Author(s):  
Juan-Manuel Schvartzman ◽  
Vincent P. Reuter ◽  
Richard P. Koche ◽  
Craig B. Thompson
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Competitive Inhibition ◽  
Mesenchymal Cells ◽  
Genome Wide ◽  
Idh Mutations ◽  
Differentiation Block

Oncogenic IDH1/2 mutations produce 2-hydroxyglutarate (2HG), resulting in competitive inhibition of DNA and protein demethylation. IDH-mutant cancer cells show an inability to differentiate but whether 2HG accumulation is sufficient to perturb differentiation directed by lineage-specifying transcription factors is unknown. A MyoD-driven model was used to study the role of IDH mutations in the differentiation of mesenchymal cells. The presence of 2HG produced by oncogenic IDH2 blocks the ability of MyoD to drive differentiation into myotubes. DNA 5mC hypermethylation is dispensable while H3K9 hypermethylation is required for this differentiation block. IDH2-R172K mutation results in H3K9 hypermethylation and impaired accessibility at myogenic chromatin regions but does not result in genome-wide decrease in accessibility. The results demonstrate the ability of the oncometabolite 2HG to block transcription factor-mediated differentiation in a molecularly defined system.

scholarly journals A Potential Role of Nuclear Matrix-associated Protein Kinase CK2 in Protection against Drug-induced Apoptosis in Cancer Cells

2000 ◽  
Vol 276 (8) ◽  
pp. 5992-5999 ◽  
Author(s):  
Chuanhai Guo ◽  
Shihui Yu ◽  
Alan T. Davis ◽  
Huamin Wang ◽  
Jeffrey E. Green ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cancer Cells ◽  
Nuclear Matrix ◽  
Protein Kinase Ck2 ◽  
Potential Role ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Kinase Ck2 ◽  
Apoptosis In Cancer Cells

scholarly journals Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis

2020 ◽  
Vol 21 (22) ◽  
pp. 8460
Author(s):  
Min Young Kim ◽  
Bowen Yan ◽  
Suming Huang ◽  
Yi Qiu
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Histone Deacetylase ◽  
Histone Deacetylases ◽  
Gene Activation ◽  
Bhlh Transcription Factor ◽  
Nucleosome Remodeling ◽  
Hdac Activity ◽  
Histone Deacetylase 1

Histone deacetylases (HDACs) play important roles in transcriptional regulation in eukaryotic cells. Class I deacetylase HDAC1/2 often associates with repressor complexes, such as Sin3 (Switch Independent 3), NuRD (Nucleosome remodeling and deacetylase) and CoREST (Corepressor of RE1 silencing transcription factor) complexes. It has been shown that HDAC1 interacts with and modulates all essential transcription factors for erythropoiesis. During erythropoiesis, histone deacetylase activity is dramatically reduced. Consistently, inhibition of HDAC activity promotes erythroid differentiation. The reduction of HDAC activity not only results in the activation of transcription activators such as GATA-1 (GATA-binding factor 1), TAL1 (TAL BHLH Transcription Factor 1) and KLF1 (Krüpple-like factor 1), but also represses transcription repressors such as PU.1 (Putative oncogene Spi-1). The reduction of histone deacetylase activity is mainly through HDAC1 acetylation that attenuates HDAC1 activity and trans-repress HDAC2 activity through dimerization with HDAC1. Therefore, the acetylation of HDAC1 can convert the corepressor complex to an activator complex for gene activation. HDAC1 also can deacetylate non-histone proteins that play a role on erythropoiesis, therefore adds another layer of gene regulation through HDAC1. Clinically, it has been shown HDACi can reactivate fetal globin in adult erythroid cells. This review will cover the up to date research on the role of HDAC1 in modulating key transcription factors for erythropoiesis and its clinical relevance.

Transcriptional control of the oxidative stress response and implications of using plant derived molecules for therapeutic interventions in cancer

2021 ◽  
Vol 28 ◽  
Author(s):  
Asim Rizvi ◽  
Mohd. Farhan ◽  
Faisal Nabi ◽  
Rizwan Hasan Khan ◽  
Mohd. Adil ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Stress Response ◽  
Cancer Cells ◽  
Transcriptional Control ◽  
Regulation Of Gene Expression ◽  
Oxidative Stress Response ◽  
Therapeutic Interventions ◽  
Lead Compounds

: Oxidative stress response is critical for the malignant cells. It plays dual role by helping cancer cells survive and proliferate but also causing apoptosis and apoptosis like cell death. The oxidative stress response is characterized by a tight regulation of gene expression by a series of transcription factors (OSRts; oxidative stress response transcription factors). In this communication, we review the role of OSRts, notably NRF2 and p53 as well as other transcription factors, that modulate the response. We discuss how the oxidative stress response is hierarchal and controls ‘live or die’ signals. This is followed by a discussion on how plant derived molecules, including polyphenols, which are described both as prooxidants and antioxidants within the cancer cells, have been reported to affect the activities of OSRts. Deriving an example from preliminary data from our group, we discuss how plant derived molecules might modulate the oxidative stress response by causing structural perturbations in the proteinacious transcription factors, notably Nrf2 and p53. We look at this information in the light of understanding how plant derived molecules maybe used as lead compounds to develop modulators of the oxidative stress response.

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