Transactivation activity of Maf nuclear oncoprotein is modulated by Jun, Fos and small Maf proteins.
The v-maf oncogene encodes a nuclear bZip protein which specifically recognizes relatively long palindromic sequences related to an AP-1 site. In this study, we investigated the relationship of transactivation and transformation activity of Maf. The amino-terminal two thirds of the molecule were dispensable for its DNA-binding activity but conferred its transactivation potential. Transactivation activities of a set of deletion mutants correlated well with their cell transforming abilities. However, a point mutant associated with enhanced oncogenic activity was not more effective in transactivation than the wild type, suggesting that some other function(s) of Maf is also important for its transforming ability. We also examined the effect of other bZip proteins on the transactivation activity of Maf. Three small Maf family proteins (MafK, MafF and MafG), which are missing the transactivation domain of v-Maf, competitively inhibited transactivation by Maf. Co-expression of Jun or Fos also affected the transactivation potential of Maf by forming Maf/Jun or Maf/Fos heterodimers of distinct DNA-binding specificities. In addition to these factors, we noticed the presence of a strong endogenous transactivating activity associated with a sequence related to an NF-E2 site rather than the typical AP-1 site in fibroblast cells. These results indicate that AP-1 site-like cis-regulatory elements of eukaryotic genes are regulated by multiple sets of bZip dimers with different DNA-binding and transactivation properties.
Kataoka
K
K
Department of Viral Oncology, Cancer Institute, Tokyo, Japan.
Noda
M
M
Nishizawa
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D016350:Leucine Zippers / Q000502:physiology*; D050985:MafK Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050985:MafK Transcription Factor; C494696:Mafk protein, mouse; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D014764:Viral Proteins; C495606:v-Maf protein, Avian retrovirus AS42; D004247:DNA