Abstract |
Several protein- nucleic acid complexes are observed when nuclear extracts from hepatoma cells are assayed for binding to the cAMP response element found in the phosphoenolpyruvate carboxykinase-cytosolic (PEPCK-C) promoter. Although cAMP response element-binding protein and CCAAT/enhancer binding proteins alpha and beta have been identified as liver factors that bind this motif, an uncharacterized, slower migrating complex was also observed. We identify activating transcription factor-2 (ATF-2) as the factor in this complex and show that ATF-2 stimulates expression from the PEPCK-C promoter. ATF-2 is a basic-leucine zipper transcription factor and a target for stress-activated protein kinases. We demonstrate that p38beta mitogen-activated protein (MAP) kinase augments ATF-2 transactivation activity on the PEPCK-C promoter, which is consistent with the interpretation that PEPCK-C promoter activity is maintained under stress through a p38 MAP kinase dependent pathway. In this regard, we show that treatment with sodium arsenite, a known activator of p38 MAP kinases, also stimulates expression from the PEPCK promoter. These results show that ATF-2 can stimulate transcription of the PEPCK-C promoter and support a role for stress inducible kinases in the maintenance of PEPCK-C expression.
|
Authors | J Cheong, J E Coligan, J D Shuman |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 273
Issue 35
Pg. 22714-8
(Aug 28 1998)
ISSN: 0021-9258 [Print] United States |
PMID | 9712902
(Publication Type: Journal Article)
|
Chemical References |
- Activating Transcription Factor 2
- Cyclic AMP Response Element-Binding Protein
- Transcription Factors
- Calcium-Calmodulin-Dependent Protein Kinases
- JNK Mitogen-Activated Protein Kinases
- Mitogen-Activated Protein Kinases
- Phosphoenolpyruvate Carboxykinase (ATP)
|
Topics |
- Activating Transcription Factor 2
- Calcium-Calmodulin-Dependent Protein Kinases
(metabolism)
- Cyclic AMP Response Element-Binding Protein
(physiology)
- Gene Expression Regulation, Enzymologic
(physiology)
- Genes, Reporter
- JNK Mitogen-Activated Protein Kinases
- Liver
(enzymology)
- Mitogen-Activated Protein Kinases
- Oxidative Stress
- Phosphoenolpyruvate Carboxykinase (ATP)
(genetics)
- Promoter Regions, Genetic
- Substrate Specificity
- Transcription Factors
(physiology)
- Transcription, Genetic
(physiology)
- Tumor Cells, Cultured
|