Transactivation of c-fos and beta-actin genes by raf as a step in early response to transmembrane signals.
A primary response to many growth factor-induced transmembrane signals is the rapid activation of transcription of the proto-oncogene c-fos and other early-response genes, including the beta-actin gene. The c-raf gene encodes a cytoplasmic serine/threonine kinase, raf-1, whose activity is also responsive to transmembrane signals and which in mutant form can transform cells. Here we show that in transient assays, the v-raf protein, which is a constitutively activated oncogenic counterpart of raf-1, can transactivate transcription from two early-response promoters, including the c-fos promoter from human and murine cells and the human beta-actin gene promoter. Multiple elements of the human fos promoter, including the dyad symmetry element necessary for growth-factor induction, an octanucleotide direct repeat element, and the region spanning the sequence from nucleotides -225 to -99 can all serve as targets for raf induction. The c-myc promoter and two adenovirus-2 early promoters are not induced. These findings indicate that raf kinase, when activated by a transmembrane signal or by mutation of a regulatory domain, can phosphorylate a factor(s) capable of regulating transcription of the c-fos and actin genes. The oncogenic form of raf may transform by constitutively activating early response protooncogenes such as c-fos.
Jamal
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S
Department of Biochemistry, New York University Medical Center, New York 10016.
Ziff
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D000199:Actins / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D005347:Fibroblasts; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D027384:Oncogene Proteins v-raf; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics*; D009053:Sarcoma Viruses, Murine / Q000235:genetics; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection
D000199:Actins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D015682:Retroviridae Proteins, Oncogenic; D015500:Chloramphenicol O-Acetyltransferase; D027384:Oncogene Proteins v-raf