Serum and v-src increase the level of a CCAAT-binding factor required for transcription from a retroviral long terminal repeat.
Transcription from the long terminal repeat (LTR) of Rous sarcoma virus (RSV) in rat 3Y1 fibroblasts was dependent on the presence of serum. Within 1 hr after addition of serum to a serum-deprived culture, there was a fivefold increase in the level of transcripts initiated at the LTR. This stimulation did not require synthesis of new proteins. The induction of transcription by serum was mostly dependent on two CCAAT boxes in the LTR. Within 1 hr after addition of serum, there was also an increase in the level of a nuclear protein that bound to the two CCAAT boxes, even in the presence of cycloheximide. This serum-induced CCAAT factor also bound CCAAT sequences from other promoters, for example, those of human heat shock protein 70, human c-Ha-ras, and human histone 1, but not to the adenovirus origin of replication or the SV40 enhancer core sequence, suggesting that it was related to CP1 or CP2. Expression from the RSV LTR was not dependent on serum in v-src-transformed cells. Using temperature-sensitive v-src, it was shown that the tyrosine kinase activity of the oncogene increased the amount of CCAAT factor that was present in the nucleus. These findings demonstrate that a basal transcription factor, the CCAAT-binding factor, could be a second messenger for transducing a primary signal from serum to the cellular transcriptional apparatus. This also suggests a pathway by which a tyrosine kinase oncogene could influence the transcription of several genes in the nucleus.
Dutta
A
A
Rockefeller University, New York, New York 10021.
Stoeckle
M Y
MY
Hanafusa
H
H
D000818:Animals; D001358:Avian Sarcoma Viruses / Q000235:genetics*; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D003470:Culture Media; D003513:Cycloheximide / Q000494:pharmacology; D004279:DNA, Viral / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D003470:Culture Media; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D003513:Cycloheximide; D011505:Protein-Tyrosine Kinases