Distinct roles of Jun : Fos and Jun : ATF dimers in oncogenesis.
Jun : Fos and Jun : ATF complexes represent two classes of AP-1 dimers that (1) preferentially bind to either heptameric or octameric AP-1 binding sites, and (2) are differently regulated by cellular signaling pathways and oncogene products. To discriminate between the functions of Jun : Fos, Jun : ATF and Jun : Jun, mutants were developed that restrict the ability of Jun to dimerize either to itself, or to Fos(-like) or ATF(-like) partners. Introduction of these mutants in chicken embryo fibroblasts shows that Jun : Fra2 and Jun : ATF2 dimers play distinct, complementary roles in in vitro oncogenesis by inducing either anchorage independence or growth factor independence, respectively. v-Jun : ATF2 rather than v-Jun : Fra2 triggers the development of primary fibrosarcomas in the chicken wing. Genes encoding extracellular matrix components seem to constitute an important subset of v-Jun : ATF2-target genes. Repression of the matrix component SPARC by Jun is essential for the induction of fibrosarcomas. Avian primary cells transformed by either Jun : Fra2 or Jun : ATF2 thus provide powerful tools for the investigation of the downstream pathways involved in oncogenesis. Further genetic studies with Jun dimerization mutants will be required to be precise and extend the specific roles of the Jun : Fos and Jun : ATF dimers during cancer progression in avian and mammalian systems.
van Dam
H
H
Department of Molecular Cell Biology, Leiden University Medical Center, Sylvius Laboratories, PO Box 9503, 2300 RA Leiden, The Netherlands.
Castellazzi
M
M
D051698:Activating Transcription Factor 2; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D019281:Dimerization; D016350:Leucine Zippers; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors