Differential regulation of CHOP-10/GADD153 gene expression by MAPK signaling in pancreatic β-cells
- 10 July 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 104 (28), 11518-11525
- https://doi.org/10.1073/pnas.0704618104
Abstract
CHOP-10 (GADD153/DDIT-3) is a bZIP protein involved in differentiation and apoptosis. Its expression is induced in response to stresses such as nutrient deprivation, perturbation of the endoplasmic reticulum, redox imbalance, and UV exposure. Here we show that CHOP expression is induced in cultured pancreatic beta-cells maintained in a basal glucose concentration of 5.5 mM and repressed by stimulatory glucose (>or=11 mM). Both induction and repression of CHOP are dependent on the MAPKs ERK1 and ERK2. Two regulatory composite sites containing overlapping MafA response elements (MARE) and CAAT enhancer binding (CEB) elements regulate transcription in an ERK1/2-dependent manner. One site (MARE-CEB), from -320 to -300 bp in the promoter, represses transcription. The other site (CEB-MARE), from +2,628 to +2,641 bp in the first intron of the CHOP gene, activates it. MafA can influence transcription of both sites. The MARE-CEB is repressed by MafA, whereas the CEB-MARE site, which is homologous to the A2C1 component of the glucose-sensitive RIPE3b region of the insulin gene promoter, is activated by MafA. These results indicate that ERK1/2 have dual roles in regulating CHOP gene expression via both promoter and intronic regions, depending on environmental and metabolic stresses imposed on pancreatic beta-cells.Keywords
This publication has 72 references indexed in Scilit:
- CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP) Regulates Osteoblast DifferentiationMolecular and Cellular Biology, 2006
- Inhibition of Glucose-Stimulated Activation of Extracellular Signal–Regulated Protein Kinases 1 and 2 by Epinephrine in Pancreatic β-CellsDiabetes, 2006
- Effect of serum on the down-regulation of CHOP-10 during differentiation of 3T3-L1 preadipocytesBiochemical and Biophysical Research Communications, 2005
- ERK1/2-dependent Activation of Transcription Factors Required for Acute and Chronic Effects of Glucose on the Insulin Gene PromoterPublished by Elsevier BV ,2005
- The diabetes-linked transcription factor PAX4 promotes β-cell proliferation and survival in rat and human isletsThe Journal of cell biology, 2004
- Induction of CHOP Expression by Amino Acid Limitation Requires Both ATF4 Expression and ATF2 PhosphorylationPublished by Elsevier BV ,2004
- Mechanism of Oxidative Stress-Induced GADD153 Gene Expression in Vascular Smooth Muscle CellsBiochemical and Biophysical Research Communications, 2002
- CHOP/GADD153 Gene Expression Response to Cellular Stresses Inhibited by Prior Exposure to Ultraviolet Light Wavelength Band C (UVC)Journal of Biological Chemistry, 2000
- The reduction of insulin gene transcription in HIT-T15 beta cells chronically exposed to high glucose concentration is associated with the loss of RIPE3b1 and STF-1 transcription factor expressionMolecular Endocrinology, 1995
- ERKs: A family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGFCell, 1991