NF-IL6, a member of the C/EBP family, regulates E1A-responsive promoters in the absence of E1A.
A cDNA encoding NF-IL6, an interleukin-6 (IL-6)-regulated human nuclear factor of the C/EBP family, is demonstrated to complement the transactivation function of E1A. The endogenous NF-IL6 level varies according to cell type and correlates positively with an IL-6-regulated cellular E1A-substituting activity that was described recently (J.M. Spergel and S. Chen-Kiang, Proc. Natl. Acad. Sci. USA 88:6472-6476, 1991). When expressed by transfection in cells which contain low levels of NF-IL6 and are incapable of complementing the function of E1A proteins, NF-IL6 also transactivates the E1A-responsive E2ae and E1B promoters, to the same magnitude as E1A. Activation by NF-IL6 is concentration dependent and sequence specific: mutational studies of the E2ae promoter suggest that the promoter-proximal NF-IL6 recognition site functions as a dominant negative regulatory site whereas the promoter-distal NF-IL6 recognition site is positively regulated at low NF-IL6 concentrations and negatively regulated when the NF-IL6 level is high. Consistent with these functions, NF-IL6 alone is sufficient to complement an E1A deletion mutant dl312 in viral infection, when expressed at appropriate concentrations. These results identify NF-IL6 as a sequence-specific cellular nuclear factor which regulates E1A-responsive genes in the absence of E1A.
Spergel
J M
JM
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029.
Hsu
W
W
Akira
S
S
Thimmappaya
B
B
Kishimoto
T
T
Chen-Kiang
S
S
D017456:Adenovirus Early Proteins; D000260:Adenoviruses, Human / Q000235:genetics*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
D017456:Adenovirus Early Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D009856:Oncogene Proteins, Viral; D015534:Trans-Activators; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase