fosB is a transforming gene encoding a transcriptional activator.
The fosB gene encodes a nuclear protein that shows a high degree of homology with c-Fos in several of the known functionally crucial domains, e.g., the leucine zipper and the DNA-binding site, but shows considerable divergence in other regions. Here, we report that FosB, when placed under the control of a constitutive promoter, exhibits clear transforming properties in focus assays using mouse NIH3T3 or rat 208F fibroblasts. The transforming potential of FosB is considerably stronger than that of a corresponding c-fos construct and resembles that of viral fos genes. Using chimeric fos/fosB constructs we show that the C-terminal half of FosB is responsible for these stronger transforming properties, apparently by giving rise to significantly higher levels of protein as compared with the corresponding c-fos sequence. Surprisingly, substitution of the N-terminus of Fos with that of FosB decreases its transforming potential. These differences in the transforming potential are not related to DNA or protein expression, but rather seem to reflect differences in the molecular function(s) encoded in the N-terminal halves of Fos and FosB protein. Both, fosB- and v-fos transformed cells show increased expression of a number of endogenous genes, including c-jun, transin, alpha 1(III) collagen and tissue plasminogen activator. Transactivation by FosB and v-fos of the c-jun and alpha 1(III) collagen gene promoters and of a 3 x TRE-tk chimeric promoter could be shown in transient CAT assays. v-Fos, but not FosB-transformed cells, also show elevated levels of urokinase and plasminogen activator inhibitor mRNAs, pointing to potential differences in the gene regulatory properties of the two Fos family members.
Schuermann
M
M
Institut für Molekularbiologie und Tumorforschung (IMT) Philipps-Universität Marburg, Federal Republic of Germany.
Jooss
K
K
Müller
R
R
D000818:Animals; D002478:Cells, Cultured; D002874:Chromosome Mapping; D003094:Collagen / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D014170:Transformation, Genetic; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D003094:Collagen; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3