NO activation of fos promoter elements requires nuclear translocation of G-kinase I and CREB phosphorylation but is independent of MAP kinase activation

• Published in: Oncogene Vol. 19; no. 54; pp. 6324 - 6333
• Main Authors: GUDI, Tanima, CASTEEL, Darren E, VINSON, Charles, BOSS, Gerry R, PILZ, Renate B
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 14.12.2000; Nature Publishing Group
• Subjects: Active Transport, Cell Nucleus; Animals; Apoptosis; Binding sites; Biological and medical sciences; c-Fos protein; Cell cycle; Cell Line; Cell Nucleus - metabolism; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; CREB protein; Cricetinae; Cyclic AMP response element-binding protein; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases - genetics; Cyclic GMP-Dependent Protein Kinases - metabolism; cyclin GMP-dependent protein kinase I; Enhancer Elements, Genetic; Fos gene; Fundamental and applied biological sciences. Psychology; Gene expression; Genes, fos; Genes, Reporter; Guanylate cyclase; Guanylate Cyclase - metabolism; Kinases; MAP kinase; MAP Kinase Signaling System; mitogen-activated protein kinase; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Molecular and cellular biology; Mutation; Nitric oxide; Nitric Oxide - physiology; Nuclear transport; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Promoter Regions, Genetic; Protein kinase; Protein kinase G; Proteins; Signal transduction; Transcription factors; Transcriptional Activation; Transfection; United States > US; California; Phosphorylation; Enzyme; Transferases; Gene expression; Binding protein; Vertebrata; Regulation(control); Cell line; Mammalia; Protein kinase; Nitric oxide; C-Onc gene; Transcription factor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1204007

We have shown that nitric oxide (NO) regulates c-fos gene expression via cGMP-dependent protein kinase (G-kinase), but NO's precise mechanism of action is unclear. We now demonstrate that: (1) NO targets two transcriptional elements in the fos promoter, i.e., the fos AP-1 binding site and the cAMP-response element (CRE); (2) NO activation of these two enhancer elements requires the CRE binding protein CREB because a dominant negative CREB fully inhibits NO transactivation of reporter genes whereas dominant negative Fos or CCAAT enhancer binding proteins have no effect; (3) CREB is phosphorylated by G-kinase in vitro and its phosphorylation increases in vivo when G-kinase is activated either directly by cGMP or indirectly by NO via soluble guanylate cyclase; (4) NO activation of fos promoter elements requires nuclear translocation of G-kinase but not activation of mitogen-activated protein kinases.