1310318

pubmed:Citation

4

Adenovirus infection of hepatoma cells inhibited transcription of the phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene and virtually eliminated transcription of a chimeric gene which contained the PEPCK promoter linked to the structural gene for chloramphenicol acetyltransferase (CAT). This effect is due to the viral protein E1A, since adenovirus containing a deletion in the E1A gene did not repress transcription from the PEPCK promoter. Both the 243R and 283R products of the E1A gene were effective. The conserved region 1 (CR-1) domain of E1A was required for this effect. Treatment of hepatoma cells with 8-bromo-cAMP or transfection with plasmids coding for the catalytic subunit of protein kinase A, CAAT/enhancer binding protein alpha (C/EBP), or Jun, all potent inducers of PEPCK gene transcription, did not relieve the inhibition caused by E1A. This inhibition does not appear to be mediated by major enhancer elements and in the PEPCK gene since transcription from the PEPCK promoter containing block mutations in binding domains for C/EBP and cAMP regulatory element binding protein (CREB) was also inhibited by E1A. Transcription of chimeric genes containing two copies each of the major cAMP response domains (CRE-1 and P-3) linked to a neutral promoter and fused to the CAT structural gene was stimulated by the catalytic subunit of protein kinase A, but this effect was totally inhibited by E1A. The strong repressive effect of E1A on PEPCK gene transcription seems to involve an interruption of an obligatory interaction between factors which bind to the cAMP response element in the PEPCK promoter and the TATA box.

eng

IM

MEDLINE

0021-9258

Print

267

NLM

2530-6

pubmed-meshheading:1310318-Adenoviridae, pubmed-meshheading:1310318-Adenovirus Early Proteins, pubmed-meshheading:1310318-CCAAT-Enhancer-Binding Proteins, pubmed-meshheading:1310318-Carcinoma, Hepatocellular, pubmed-meshheading:1310318-Chloramphenicol O-Acetyltransferase, pubmed-meshheading:1310318-Cyclic AMP, pubmed-meshheading:1310318-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:1310318-DNA-Binding Proteins, pubmed-meshheading:1310318-Gene Expression Regulation, Enzymologic, pubmed-meshheading:1310318-Gene Expression Regulation, Viral, pubmed-meshheading:1310318-Mutation, pubmed-meshheading:1310318-Nuclear Proteins, pubmed-meshheading:1310318-Oncogene Proteins, Viral, pubmed-meshheading:1310318-Phosphoenolpyruvate Carboxykinase (GTP), pubmed-meshheading:1310318-Promoter Regions, Genetic, pubmed-meshheading:1310318-Protein Kinases, pubmed-meshheading:1310318-Proto-Oncogene Proteins c-jun, pubmed-meshheading:1310318-TATA Box, pubmed-meshheading:1310318-Transcription, Genetic, pubmed-meshheading:1310318-Transcription Factors, pubmed-meshheading:1310318-Tumor Cells, Cultured

Adenovirus E1A represses the cyclic AMP-induced transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in hepatoma cells.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't