scholarly journals Subtype-selective Interaction with the Transcription Factor CCAAT/Enhancer-binding Protein (C/EBP) Homologous Protein (CHOP) Regulates Cell Surface Expression of GABABReceptors

2005 ◽  
Vol 280 (39) ◽  
pp. 33566-33572 ◽  
Author(s):  
Kathrin Sauter ◽  
Thomas Grampp ◽  
Jean-Marc Fritschy ◽  
Klemens Kaupmann ◽  
Bernhard Bettler ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Surface ◽  
Protein C ◽  
Binding Protein ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Homologous Protein ◽  
Enhancer Binding Protein ◽  
Selective Interaction ◽  
Subtype Selective

scholarly journals Induction of CCAAT/Enhancer-binding Protein (C/EBP)-homologous Protein/Growth Arrest and DNA Damage-inducible Protein 153 Expression during Inhibition of Phosphatidylcholine Synthesis Is Mediated via Activation of a C/EBP-activating Transcription Factor-responsive Element

2004 ◽  
Vol 279 (50) ◽  
pp. 52007-52015 ◽  
Author(s):  
Michiel H. M. van der Sanden ◽  
Henriët Meems ◽  
Martin Houweling ◽  
J. Bernd Helms ◽  
Arie B. Vaandrager
Keyword(s):  
Dna Damage ◽  
Transcription Factor ◽  
Protein C ◽  
Binding Protein ◽  
Growth Arrest ◽  
Homologous Protein ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Inducible Protein ◽  
Responsive Element

The gene for the proapoptotic transcription factor CCAAT/enhancer-binding protein (C/EBP)-homologous protein/growth arrest and DNA damage-inducible protein 153 (CHOP/GADD153) is induced by various cellular stresses. Previously, we described that inhibition of phosphatidylcholine (PC) synthesis in MT58 cells, which contain a temperature-sensitive mutation in CTP:phosphocholine cytidylyltransferase (CT), results in apoptosis preceded by the induction of CHOP. Here we report that prevention of CHOP induction, by expression of antisense CHOP, delays the PC depletion-induced apoptotic process. By mutational analysis of the conserved region in the promoter of the CHOP gene, we provide evidence that the C/EBP-ATF composite site, but not the ER stress-responsive element or the activator protein-1 site, is required for the increased expression of CHOP during PC depletion. Inhibition of PC synthesis in MT58 cells also led to an increase in phosphorylation of the stress-related transcription factor ATF2 and the stress kinase JNK after 8 and 16 h, respectively. In contrast, no phosphorylation of p38 MAPK was observed in MT58 cultured at the nonpermissive temperature. Treatment of MT58 cells with the JNK inhibitor SP600125 could rescue the cells from apoptosis but did not inhibit the phosphorylation of ATF2 or the induction of CHOP. Taken together, our results suggest that increased expression of CHOP during PC depletion depends on a C/EBP-ATF element in its promoter and might be mediated by binding of ATF2 to this element.

scholarly journals Obesity-Linked Variants of Melanocortin-4 Receptor Are Misfolded in the Endoplasmic Reticulum and Can Be Rescued to the Cell Surface by a Chemical Chaperone

2010 ◽  
Vol 31 (4) ◽  
pp. 605-605
Author(s):  
Susana Granell ◽  
Sameer Mohammad ◽  
Ramanagouda Ramanagoudr-Bhojappa ◽  
Giulia Baldini
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
Er Stress ◽  
Binding Protein ◽  
Intracellular Localization ◽  
Specific Inhibitor ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Chemical Chaperone ◽  
Melanocortin 4 Receptor

Abstract Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed in the brain where it controls food intake. Many obesity-linked MC4R variants are poorly expressed at the plasma membrane and are retained intracellularly. We have studied the intracellular localization of four obesity-linked MC4R variants, P78L, R165W, I316S, and I317T, in immortalized neurons. We find that these variants are all retained in the endoplasmic reticulum (ER), are ubiquitinated to a greater extent than the wild-type (wt) receptor, and induce ER stress with increased levels of ER chaperones as compared with wt-MC4R and appearance of CCAAT/enhancer-binding protein homologous protein. Expression of the X-box-binding-protein-1 with selective activation of a protective branch of the unfolded protein response did not have any effect on the cell surface expression of MC4R-I316S. Conversely, the pharmacological chaperone 4-phenyl butyric acid (PBA) increased the cell surface expression of wt-MC4R, MC4R-I316S, and I317T by more than 40%. PBA decreased ubiquitination of MC4R-I316S and prevented ER stress induced by expression of the mutant, suggesting that the drug functions to promote MC4R folding. MC4R-I316S rescued to the cell surface is functional, with a 52% increase in agonist-induced cAMP production, as compared with untreated cells. Also direct inhibition of wt-MC4R and MC4R-I316S ubiquitination by a specific inhibitor of the ubiquitin-activating enzyme 1 increased by approximately 40% the expression of the receptors at the cell surface, and the effects of PBA and ubiquitin-activating enzyme 1 were additive. These data offer a cell-based rationale that drugs that improve MC4R folding or decrease ER-associated degradation of the receptor may function to treat some forms of hereditary obesity.

scholarly journals CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter.

1996 ◽  
Vol 16 (3) ◽  
pp. 1231-1240 ◽  
Author(s):  
D E Zhang ◽  
C J Hetherington ◽  
S Meyers ◽  
K L Rhoades ◽  
C J Larson ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Protein C ◽  
Binding Protein ◽  
Colony Stimulating Factor ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Transcription factors play a key role in the development and differentiation of specific lineages from multipotential progenitors. Identification of these regulators and determining the mechanism of how they activate their target genes are important for understanding normal development of monocytes and macrophages and the pathogenesis of a common form of adult acute leukemia, in which the differentiation of monocytic cells is blocked. Our previous work has shown that the monocyte-specific expression of the macrophage colony-stimulating factor (M-CSF) receptor is regulated by three transcription factors interacting with critical regions of the M-CSF receptor promoter, including PU.1 and AML1.PU.1 is essential for myeloid cell development, while the AML1 gene is involved in several common leukemia-related chromosome translocations, although its role in hematopoiesis has not been fully identified. Along with AML1, a third factor, Mono A, interacts with a small region of the promoter which can function as a monocyte-specific enhancer when multimerized and linked to a heterologous basal promoter. Here, we demonstrate by electrophoretic mobility shift assays with monocytic nuclear extracts, COS-7 cell-transfected factors, and specific antibodies that the monocyte-enriched factor Mono A is CCAAT enhancer-binding protein (C/EBP). C/EBP has been shown previously to be an important transcription factor involved in hepatocyte and adipocyte differentiation; in hematopoietic cells, C/EBP is specifically expressed in myeloid cells. In vitro binding analysis reveals a physical interaction between C/EBP and AML1. Further transfection studies show that C/EBP and AML1 in concert with the AML1 heterodimer partner CBF beta synergistically activate M-CSF receptor by more then 60 fold. These results demonstrate that C/EBP and AML1 are important factors for regulating a critical hematopoietic growth factor receptor, the M-CSF receptor, suggesting a mechanism of how the AML1 fusion protein could contribute to acute myeloid leukemia. Furthermore, they demonstrate physical and functional interactions between AML1 and C/EBP transcription factor family members.

Regulation of the cell-surface expression of an HTLV-I binding protein in human T cells during immune activation

Blood ◽  
2003 ◽  
Vol 101 (8) ◽  
pp. 3085-3092 ◽  
Author(s):  
Manisha D. Nath ◽  
Francis W. Ruscetti ◽  
Cari Petrow-Sadowski ◽  
Kathryn S. Jones
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cell Lines ◽  
Cd4 T Cells ◽  
Binding Protein ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Type I ◽  
Primary Cells

AbstractLittle is known about the requirements for human T-cell leukemia virus type I (HTLV-I) entry, including the identity of the cellular receptor(s). Recently, we have generated an HTLV-I surface glycoprotein (SU) immunoadhesin, HTSU-IgG, which binds specifically to cell-surface protein(s) critical for HTLV-I–mediated entry in cell lines. Here, expression of the HTLV-I SU binding protein on primary cells of the immune system was examined. The immunoadhesin specifically bound to adult T cells, B cells, NK cells, and macrophages. Cell stimulation dramatically increased the amount of binding, with the highest levels of binding on CD4+ and CD8+ T cells. Naive (CD45RAhigh, CD62Lhigh) CD4+ T cells derived from cord blood cells, in contrast to other primary cells and all cell lines examined, bound no detectable HTLV-I SU. However, following stimulation, the level of HTSU-IgG binding was rapidly induced (fewer than 6 hours), reaching the level of binding seen on adult CD4+ T cells by 72 hours. In contrast to HTLV-I virions, the soluble HTSU-IgG did not effect T-cell activation or proliferation. When incubated with human peripheral blood mononuclear cells in a mixed leukocyte reaction, HTSU-IgG inhibited proliferation at less than 1 ng/mL. These results indicate that cell-surface expression of the HTLV SU binding protein is up-regulated during in vitro activation and suggest a role for the HTLV-I SU binding proteins in the immunobiology of CD4+ T cells.

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