Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation.
The Jun and Fos oncoproteins belong to the AP-1 family of transcriptional activators and are believed to induce cellular transformation by inappropriately activating genes involved in cell replication. To determine whether transcriptional activation through AP-1 sites is sufficient for transforming activity, we examined the properties of an autonomous and heterologous AP-1 protein, yeast GCN4, in rat embryo fibroblasts. GCN4 induces transcriptional activation through AP-1 sites but, unlike Jun and Fos, fails to induce cellular transformation, in cooperation with Ha-ras. Jun-GCN4 and Fos-GCN4 homodimers independently induce cellular transformation indicating that the amino-terminal regions of Jun and Fos each contain regulatory functions that are required for oncogenesis but are distinct from generic transcriptional activation domains. In addition, these observations have implications for the nature of the oncogenically relevant target genes that respond to Jun and Fos.
Oliviero
S
S
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Robinson
G S
GS
Struhl
K
K
Spiegelman
B M
BM
D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011494:Protein Kinases