Transformation and transactivation suppressor activity of the c-Jun leucine zipper fused to a bacterial repressor.
Transcription factor c-Jun appears to be a nuclear target of the Ras-induced signal transduction pathway. In fact, some experiments show that transforming forms of the Ras protein cooperate with Jun in transcriptional activation mediated by an AP-1 site and others indicate that the two oncoproteins cooperate in cellular transformation. Although it is likely that intracellular signaling systems activated by Ras might act directly on c-Jun by inducing specific phosphorylation, it is unclear how c-Jun participates in the transformation process. Here, we present results obtained with a LexA-Jun zipper fusion that lacks both the transcriptional activation domains and the basic region of the DNA-binding domain of c-Jun and contains only the intact leucine-zipper domain. This fusion product has a dominant negative effect on the transcriptional activation elicited by phorbol esters, c-Jun, c-Fos, Ras and E1A on an AP-1-responsive site. An analogous LexA-Fos zipper fusion has similar effects on transcriptional induction. The LexA-Jun zipper fusion acts further as a transformation suppressor, since it causes the generation of nontransformed revertants of ras-transformed cells. This effect is likely to be elicited by the dimerization potential of the Jun leucine zipper trapping cellular Jun and/or Fos in a protein complex unable to bind to DNA. These data implicate further that Ras-mediated transformation involves functional transcription factor AP-1 and that it is possible to interfere with cell transformation by interfering simply with the dimerization of transcription factors involved in the transformation process.
Granger-Schnarr
M
M
Institut de Biologie Moléculaire et Cellulaire du Centre Nationale de la Recherche Scientifique, Strasbourg, France.
Benusiglio
E
E
Schnarr
M
M
Sassone-Corsi
P
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002822:Choriocarcinoma; D004926:Escherichia coli / Q000235:genetics; D005809:Genes, Regulator / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016296:Mutagenesis; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015183:Restriction Mapping; D012697:Serine Endopeptidases; D013489:Suppression, Genetic; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D000099160:LexA Repressor Protein
D001426:Bacterial Proteins; D015500:Chloramphenicol O-Acetyltransferase; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D012697:Serine Endopeptidases; D013755:Tetradecanoylphorbol Acetate; D000099160:LexA Repressor Protein