The CCAAT/enhancer (C/EBP) family of basic-leucine zipper (bZIP) transcription factors is a multifaceted highly-regulated system for gene regulation
ABSTRACT The C/EBP family of proteins represents an important group of bZIP transcription factors that are key to the regulation of essential functions such as cell cycle, hematopoiesis, skeletal development, and host immune responses. They are also intimately associated with tumorigenesis and viral disease. These proteins are regulated at multiple levels, including gene induction, alternative translational initiation, post-translational modification, and protein-protein interaction. This review attempts to integrate recent reports with more than 20 years of previous effort focused on this fascinating collection of regulators.
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- "Specifically, in all isoforms of C/EBP, an extension of the zipper dimerization domain, the tail sequence, acts as a motif for protein-protein interactions. For a detailed description of the structure of CCAAT/enhancer binding family members, we refer to two earlier reviews  . "
ABSTRACT: The prevalence of the metabolic syndrome and underlying metabolic disturbances increase rapidly in developed countries. Various molecular targets are currently under investigation to unravel the molecular mechanisms that cause these disturbances. This is done in attempt to counter or prevent the negative health consequences of the metabolic disturbances. Here, we reviewed the current knowledge on the role of C/EBP-β in these metabolic disturbances. C/EBP-β deletion in mice resulted in downregulation of hepatic lipogenic genes and increased expression of β-oxidation genes in brown adipose tissue. Furthermore, C/EBP-β is important in the differentiation and maturation of adipocytes and is increased during ER stress and proinflammatory conditions. So far, studies were only conducted in animals and in cell systems. The results found that C/EBP-β is an important transcription factor within the metabolic disturbances of the metabolic system. Therefore, it is interesting to examine the potential role of C/EBP-β at molecular and physiological level in humans.BioMed Research International 01/2015; 2015:324815. DOI:10.1155/2015/324815 · 2.71 Impact Factor
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- "C / EBP proteins are a well known recipient of extracellular signals resulting in multiple phosphorylations , acetylations , and SUMOylations ( Nerlov , 2008 ) . Up to eight different phosphorylation sites have been described in C / EBPa ( Tsukada et al . , 2011 ) , and therefore the investigation of the precise phosphorylated forms involved in SHP regulation is complex and out of the scope of this paper ."
ABSTRACT: The small heterodimer partner (SHP, NR0B2) is an atypical nuclear receptor that lacks DNA-binding domain. It interacts with and inhibits many transcription factors, affecting key metabolic processes including bile acid, cholesterol, fatty acid and drug metabolism. Our aim was to determine the influence of steatotic drugs and non-alcoholic fatty liver disease (NAFLD) on SHP expression, and to investigate the potential mechanisms. SHP was found repressed by steatotic drugs (valproate, doxycycline, tetracycline and cyclosporin A) in cultured hepatic cells, and in the livers of different animal models of NAFLD: iatrogenic (tetracycline treated rats), genetic (glycine N-methyltransferase deficient mice) and nutritional (mice fed a methionine and choline deficient diet). Among the different transcription factors investigated, CCAAT-enhancer-binding protein α (C/EBPα) showed the strongest dominant-repressive effect on SHP expression in HepG2 and human hepatocytes. Reporter assays revealed that the inhibitory effect of C/EBPα and steatotic drugs co-localize between -340 and -509 bp of the SHP promoter and mutation of a predicted C/EBPα response element at -473 bp abolished SHP repression by both C/EBPα and drugs. Moreover, inhibition of major stress signaling pathways demonstrated that the mitogen-activated protein kinase kinase 1/2 pathway activates while the phosphatidylinositol 3 kinase pathway represses SHP in a C/EBP-dependent manner. We conclude that SHP is downregulated by several steatotic drugs and in advanced NAFLD. These conditions can activate signals that target C/EBPα and consequently repress SHP, thus favoring the progression and severity of NAFLD. The American Society for Pharmacology and Experimental Therapeutics.Molecular pharmacology 01/2015; 87(4). DOI:10.1124/mol.114.096313 · 4.13 Impact Factor
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- "In order to annotate the presence of putative C/EBPα binding sites in the promoter of differentially expressed genes, we used previously generated ChIP data sets for CEBPB (C/EBPβ) and CEBPD (C/EBPδ) in K562 cells , which exhibit identical DNA-binding specificities with C/EBPα . We found several coding and non-coding differentially expressed genes bound by either CEBPB or CEBPD in their putative promoter region within a distance of −5 kb from the TSS (Figure 1B and Additional file 1, Additional file 7: Figure S3, Additional file 8: Table S4, Additional file 9: Table S5, Additional file 10: Table S6 and Additional file 11: Table S7). "
ABSTRACT: CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation. Disruption of CEBPA function contributes to the development of acute myeloid leukemia (AML). CEBPA regulates a large number of protein coding genes of which several were shown to contribute to CEBPA function. In this study, we expand the analysis of CEBPA transcriptional targets to the newly identified class of long non-coding RNAs. We show that lncRNAs are a main component of the transcriptional program driven by C/EBPα and that many of these are also induced during granulocytic differentiation of AML cell lines supporting their relevance in proliferation arrest and differentiation. Electronic supplementary material The online version of this article (doi:10.1186/s13045-014-0069-1) contains supplementary material, which is available to authorized users.Journal of Hematology & Oncology 09/2014; 7(1):69. DOI:10.1186/s13045-014-0069-1 · 4.81 Impact Factor