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Activating transcription factor-2 regulates phosphoenolpyruvate carboxykinase transcription through a stress-inducible mitogen-activated protein kinase pathway.

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.
AuthorsJ Cheong, J E Coligan, J D Shuman
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 273 Issue 35 Pg. 22714-8 (Aug 28 1998) ISSN: 0021-9258 [Print] United States
PMID9712902 (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

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