Interleukin 6 enhances a cellular activity that functionally substitutes for E1A protein in transactivation.
An interleukin 6 (IL-6)-regulated cellular activity in HepG2 cells is found to functionally substitute for the transcriptional transactivator product of the adenovirus transforming gene E1A in transactivating E1A-dependent and E1A-responsive viral early genes. Mutant viruses deficient in E1A expression replicate in HepG2 cells. Induction with IL-6 leads to significant enhancement of synthesis of viral early E1B and E2ae mRNAs by greater than 30-fold and increases viral replication to the wild-type levels. The E1A-substituting activity activates E1A-responsive promoters in transient transfection, and this transcriptional activity is regulated by IL-6 induction. Formation of distinct protein-promoter complexes by binding of proteins in nuclear extracts prepared from HepG2 cells to the E1A-dependent E2ae promoter further supports the possibility that this activity may be a nuclear component in the IL-6 signal transduction pathway.
Spergel
J M
JM
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029.
Chen-Kiang
S
S
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000502:physiology; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005333:Fetus; D005814:Genes, Viral; D006367:HeLa Cells / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000502:physiology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000187:drug effects
D017456:Adenovirus Early Proteins; D004273:DNA, Neoplasm; D004279:DNA, Viral; D015850:Interleukin-6; D015345:Oligonucleotide Probes; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors