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Proto-Oncogene and Onco-Suppressor Gene Expression
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The p53 antigen is a 53-kDa nuclear phosphoprotein that is involved in the regulation of events related to the cell cycle in both normal and transformed cells.334-340 Growth arrest induced by p53 occurs prior to or near a restriction point, the R point, in late Gl phase of the cycle and may be affected by the repression of the expression of a specific subset of genes, in particular the c-myb proto-oncogene and the DNA polymerase-α gene.341 The wild-type p53 protein is an unusually shaped tetramer that binds directly to DNA.342 The p53 protein contains a domain that is involved in the regulation of transcription through the recognition of a consensus palindrome sequence in the DNA.343 Wild-type p53 protein binds to the TATA-binding protein and represses transcription.344 Upon binding DNA, wild-type p53 changes conformation at both its amino- and carboxyl-terminal regions.345 Transcription from the human HSP70promoter is repressed by p53, and this effect is mediated by a CCAAT binding factor (CBF). Thus, protein-protein interaction between p53 and specific transcription factors may be a mechanism by which p53 regulates gene expression.346
Scientific Basis of Male Hypogonadism
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Thang S. Han, Pierre-Marc G. Bouloux
The unliganded AR is stabilized by its association with a heat shock protein (HSP 90) acting as a molecular chaperone. Binding of testosterone or DHT to AR induces a conformational change, causing AR to dissociate from HSP 90, thereby becoming activated. The ligand-bound AR dimerizes, which increases its DNA-binding activity. The dimerized AR tandems target specific DNA sections of androgen response elements (AREs) in the promoter region of the androgen-sensitive genes, thereby initiating gene transcription. The first zinc finger is responsible for specificity of DNA binding. The second zinc finger stabilizes AR binding. Binding of AR to DNA influences transcription of androgen-sensitive genes, which lie downstream (3′) of the AREs. The transcriptional activity of the AR involves recruitment of coactivators that link AR to components of the transcription machinery such as RNA-polymerase II (RNA-Pol II), TATA box-binding protein (TBP), TBP-associating factors, and general transcription factors. This communication triggers mRNA and protein synthesis, which consequently results in an androgen response (Fig. 9).
Cisplatin and Related Anticancer Drugs: Recent Advances and Insights
Published in Astrid Sigel, Helmut Sigel, Metal Ions in Biological Systems, 2004
Katie R. Barnes, Stephen J. Lippard
The TATA-binding protein (TBP) also selectively binds to cisplatin-modified DNA. In fact, of all known platinated-DNA binding proteins, TBP has the highest specificity for platinum-damaged DNA [74,75]. TBP binds to the TATA box located 30 bp upstream from a transcription start site and recruits other vital transcription factors [75]. Inhibition of transcription by cisplatin can be restarted upon addition of TBP, suggesting that platinum-DNA adducts are able to ‘hijack’ TBP from its natural binding sites [75]. Platination of DNA containing a TATA-box significantly increases the binding affinity of TBP. The enhancement of TBP affinity is maximized when the platinum adduct is positioned near the intercalation site of the TBP phenylalanine [75]. The flanking sequence dependence of TBP is similar to that of HMGB 1. In particular, having the flexible A·T bp flanking the platinum adduct site enhances TBP binding affinity [74]. TBP very slowly associates to and dissociates from both cisplatin-modified DNA and the TATA box [76]. Consequently, TBP is only able to shield cisplatin-adducts from nucleotide excision repair when allowed first to form the protein-DNA complex before exposure to the repair machinery.
Aging influence on pulmonary and systemic inflammation and neural metabolomics arising from pulmonary multi-walled carbon nanotube exposure in apolipoprotein E-deficient and C57BL/6 female mice
Published in Inhalation Toxicology, 2023
Tamara L. Young, David Scieszka, Jessica G. Begay, Selita N. Lucas, Guy Herbert, Katherine Zychowski, Russell Hunter, Raul Salazar, Andrew K. Ottens, Aaron Erdely, Haiwei Gu, Matthew J. Campen
Mouse cerebrovascular endothelial cells (mCEC) were obtained from a commercial vendor (Cell Biologics, Chicago, IL) and maintained according to manufacturer’s recommendations at 37 °C and 5% CO2 with complete endothelial cell medium supplemented with 5% fetal bovine serum. All experiments were conducted with cells between passages 3 and 8. To determine the serum cumulative inflammatory potential of MWCNT exposure, MBECs were treated with serum isolated from MWCNT-exposed and control mice as previously described (Cung et al. 2015; Zychowski et al. 2016). Briefly, MBECs were serum-starved overnight then incubated in FBS-free culture media supplemented at a final concentration of 5% v/v serum from control (0 μg) or 40 μg MWCNT exposed mice for 4 h and harvested. RNA was isolated using the RNeasy Mini Kit (QIAGEN, Germantown, MD), and reverse transcribed prior to gene expression analyses via quantitative real-time PCR (qPCR). Expression of mouse Ccl2 (Mm00441242_m1), Icam1 (Mm00516023_m1), Il6 (Mm00446190-m1), Tnfa (Mm00443258_m1), Tgfb (Mm01178820_m1), and Vcam1 (Mm01320970_m1) (Applied Biosystems, Foster City, CA) was measured using the TaqmanR Gene Expression protocol (ThermoScientific, Waltham, MA) following the manufacturer’s instructions. Relative gene expression normalized to the endogenous gene expression control TATA-Box Binding Protein (TBP) (Mm00446973_m1) gene was determined using the 2−ΔΔCT method for all samples with threshold cycle values (CT) under 35. Results are expressed as fold change.
Sex differences in the hypothalamic-pituitary-adrenal axis response following a single or multiple days of sleep restriction
Published in Stress, 2020
Katelyn N. Buban, Elizabeth A. Shupe, Stephen W. Rothwell, T. John Wu
Relative mRNA expression in the pituitary (proopiomelanocortin (Pomc), corticotropin releasing factor receptor 1 (Crfr1), mineralocorticoid receptor (MR), and glucocorticoid receptor (GR)) and adrenal glands (11β-hydroxylase (11β-OHase)and melanocortin 2 receptor (Mc2r)) was measured by RT-qPCR as previously described (Russell et al., 2018). Each sample was assayed in duplicate using the iQ SYBR Green Supermix (Cat. No. 1708884, Bio-Rad, Hercules, CA) and the respective primer pairs on the CFX Connect Real-time System (Bio-Rad). Each run consisted of an initial denaturation and enzyme activation at 95 °C for 3 min, followed by 40 cycles of denaturation (95 °C, 15 s), annealing (60 °C, 30 s) and extension (72 °C, 30 s). Melt curve analysis was performed after each reaction to ensure a single amplicon. All primer sequences for the pituitary and adrenal glands were designed and verified using NCBI BLAST (Table 1). Relative expression of each gene was determined using the delta delta Ct (ΔΔCt) method. All data was normalized to the expression of the TATA-binding protein (Livak & Schmittgen, 2001; Pfaffl, 2001; Schmittgen & Livak, 2008) and expressed relative to the male control group.
Ribosomopathies and cancer: pharmacological implications
Published in Expert Review of Clinical Pharmacology, 2022
Gazmend Temaj, Sarmistha Saha, Shpend Dragusha, Valon Ejupi, Brigitta Buttari, Elisabetta Profumo, Lule Beqa, Luciano Saso
The preinitiation complex consists of upstream binding factors (UBF), a selective factor (SL1, known as TIF1-B), transcription initiation factor 1A (TIF1A), and Pol I. UBF marks the promoter region by binding to the core promoter that surrounds the transcription start site. SL1 is then recruited to the promoter and directs promoter-specific transcription initiation. Functional interactions among UBF, SL1, and the human rRNA promoter are fundamental for promoter function and rRNA synthesis. Recruitment of the TATA-binding protein-TAFI complex SL1 to human ribosomal DNA promoters is mediated by the carboxyl-terminal activation domain of UBF, which is regulated by UBF phosphorylation [34]. TIF-1A interacts with Pol-I, which is essential for PIC formation [35,36].