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Regulation of C-Reactive Protein, Haptoglobin, and Hemopexin Gene Expression
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Dipak P. Ramji, Riccardo Cortese, Gennaro Ciliberto
IL-6DBP belongs to the C/EBP class of transcription factors. These proteins are positive regulators of gene transcription and bind DNA as dimers. Their DNA binding domain consists of a dimerization interface, termed the leucine zipper, and a DNA contact surface containing clusters of basic amino acid residues. Several members of this family have recently been cloned and show substantial homology in their DNA binding domain (Figure 15). These include: C/EBP (C/EBPα),79,87 IL-6DBp (NF-IL-6,77 LAP,88 AGP/EBP,89 CRP2,90 and C/EBPβ85), and Ig/EBP-1104 (C/EBPγ), CRP1,90 and C/EBPδ.85) With the exception of Ig/EBP-1, which is expressed ubiquitously,104 the other members show a restricted, but partially overlapping, expression pattern in different tissues.85,88,90 The different members are capable of forming heterodimers in all intrafamilial combinations.85,88,90,104 Thus, heterodimeric interactions between the different members may potentially play an important role in the modulation of AP gene transcription. Indeed, functional interaction between IL-6DBP and C/EBP has been demonstrated (Section III.H). In the presence of equimolar amounts of IL-6DBPand C/EBP, the latter, which normally activates transcription in an IL-6-independent manner, is recruited into heterodimers whose activity is regulated by IL-6.
Cytokine Regulation of Cholangiocyte Growth
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
IL-6 is a member of a family of broadly acting cytokines whose cognate receptors share the common signal-transducing component gp130.16 This family includes leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNF), IL-11, cardiotrophin-1 (CT-1) and oncostatin M. IL-6 interacts sequentially with two receptor subunits with distina functions, the ligand binding subunit IL6R (gp80) and the signal transducing chain gpl30, and assembles a hexameric receptor complex formed by two IL6/two IL6R and two gpl30 molecules.16 Double transgenic mice expressing both human IL-6 and a soluble form of IL-6R develop dramatic liver specific abnormalities including a prominent liver nodular hyperplasia further emphasizing the involvement of IL-6 in hepatic pathophysiology. Signal transduction in response to IL-6 occurs primarily via two well-defined pathways: (a) the Ras/Mitogen Activated Protein Kinase (MAPK) pathway and (b) the Jak/Stat pathway.16 Induction of these pathways results in the enhanced activity of a set of transcription factors that specifically mediate the increased expression of the acute phase reactants: C/EBPβ/NF-IL6 and C/EBPδ are activated via the Ras/MAPK pathway, while the Stat3/APRF is activated by the Jak/Stat pathway.
B-Lymphoblastic Leukemia/Lymphoma
Published in Wojciech Gorczyca, Atlas of Differential Diagnosis in Neoplastic Hematopathology, 2014
Akasaka et al. [53] described a new subgroup of B-ALL with IGH translocations involving CEBP gene family, which included patients with t(8;14)(q11;q32) involving CEBPD on chromosome 8, t(14;19)(q32;q13) involving CEBPA, inv(14) (q11q32) or t(14;14)(q11;q32) involving CEBPE, and t(14;20) (q32;q13) involving CEBPB.
Integrative exploration of the mutual gene signatures and immune microenvironment between benign prostate hyperplasia and castration-resistant prostate cancer
Published in The Aging Male, 2023
Fei Wu, Hao Ning, Yang Sun, Haihu Wu, Jiaju Lyu
To further understand the driving force of transcriptomic changes between BPH and CaP, the activity of transcriptional factors (TFs) was screened across scRNA-seq datasets. Of all the TFs regulons (TFs and their target genes), most of them were generally active in both BPH and CaP. Here, the relatively exclusive TFs were selected and visualized in a heatmap (Figure 3(A)). To be more specific in the location of cell types, feature plots of TFs activity indicated that FOSL1 and MYC were activated explicitly in BPH, but not normal prostate or CaP (Figure 3(B–D)). SPDEF was exclusively activated in luminal cells of CaP (Figure 3(B,E)). CEBPD and ELF3 were more active in normal prostate, compared with BPH or CaP, while XBP1 was suppressed in normal prostate, but not BPH or CaP (Figure 3(B)). The G.O. analysis of shared genes between the BPH regulons and modules indicated that the cytokines signaling pathway was the most significantly enriched (Figure S2). In addition, lipid metabolism and histone deacetylation were dominantly enriched in the prostate cancer group (Figure S3).
Targeting Autophagy In Disease: Recent Advances In Drug Discovery
Published in Expert Opinion on Drug Discovery, 2020
Dasol Kim, Hui-Yun Hwang, Ho Jeong Kwon
C/EBP family members (C/EBPα, C/EBPβ, C/EBPγ, C/EBPδ, C/EBPε, and C/EBPζ) are characterized by a conserved b-Zip domain at the C-terminus that mediates dimerization and DNA binding [36]. C/EBP family members are known to regulate cell proliferation and differentiation at the transcriptional level [37]. Recent studies have revealed that they also have a role in autophagic regulation. Among them, C/EBPβ was reported to control the expression of autophagy genes, including Beclin-1, ATG5, and ATG4 [38,39]. More recently, C/EBPδ (CEBPD) was found to activate transcription of the autophagy genes LC3B and ATG3 in hepatocellular carcinoma (HCC) [40]. Another transcription factor, C/EBPζ (C/EBP-homologous protein/CHOP), alone or in combination with ATF4, was revealed to bind the promoter regions of a set of autophagy genes through eIF2α/ATF4 pathway activation under ER stress or starvation conditions, thereby regulating autophagy [41]. Thus, the C/EBP family can regulate cellular homeostasis as autophagy master genes, supporting their utility as molecular targets for related diseases.
TCF7L2 Expression Is Regulated by Cell Differentiation and Overfeeding in Human Adipose Tissue
Published in Endocrine Research, 2019
Louise Justesen, Rasmus Ribel-Madsen, Linn Gillberg, Ninna S. Hansen, Anne Louise Wulff, Louise G. Grunnet, Charlotte Brøns
Total RNA was extracted from tissue biopsies or cell cultures, and transcriptome-wide expression performed using the GeneChip Human Gene 1.0 ST (Affymetrix, Santa Clara, CA, USA)22 or Human Expression HT-12 v4 (Illumina, San Diego, CA, USA)18 arrays as previously described.18,22 For both the Affymetrix array and the Illumina array TCF7L2 was represented by one probe (Illumina ID 6900491). FABP4, LEP, PPARG, CEBPA, CEBPB and CEBPD were chosen as markers for adipocyte differentiation similarly to our previous study of adipose tissue progenitor cells.19