1. AP-1 dimers regulate transcription of the p14/p19ARF tumor suppressor gene
- Author
-
Maya Ameyar-Zazoua, Marta B. Wisniewska, Erwin F. Wagner, Moshe Yaniv, Latifa Bakiri, Jonathan B. Weitzman, Expression Génétique et Maladies (EGM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Research Institute of Molecular Pathology (IMP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: DNA Primers ,Cancer Research ,Tumor suppressor gene ,Transcription, Genetic ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,MESH: Base Sequence ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,03 medical and health sciences ,Mice ,0302 clinical medicine ,p14arf ,Downregulation and upregulation ,Transcription (biology) ,Tumor Suppressor Protein p14ARF ,Genetics ,Transcriptional regulation ,medicine ,Animals ,MESH: Animals ,Genes, Tumor Suppressor ,MESH: Tumor Suppressor Protein p14ARF ,Promoter Regions, Genetic ,MESH: Mice ,Molecular Biology ,Gene ,Cyclin-Dependent Kinase Inhibitor p16 ,030304 developmental biology ,DNA Primers ,0303 health sciences ,Base Sequence ,MESH: Transcription, Genetic ,MESH: Polymerase Chain Reaction ,Promoter ,MESH: Genes, Tumor Suppressor ,Molecular biology ,MESH: Transcription Factor AP-1 ,Cell biology ,Transcription Factor AP-1 ,MESH: Promoter Regions (Genetics) ,MESH: Dimerization ,MESH: Cyclin-Dependent Kinase Inhibitor p16 ,030220 oncology & carcinogenesis ,Carcinogenesis ,Dimerization - Abstract
Evidence is accumulating about the role of individual AP-1 components in cell proliferation and transformation. Notably, Ras-mediated transformation is characterized by the upregulation of particular AP-1 members, such as c-Jun and Fra-1. The p14/p19ARF tumor suppressor gene is a key link between oncogenic Ras signaling and the p53 pathway. We explored the involvement of AP-1 dimers in the transcriptional regulation of the p14/p19ARF gene. We demonstrate that both the human and mouse ARF promoters are transcriptional targets of selective AP-1 dimers. The ARF promoter is regulated specifically by AP-1 heterodimers containing Fra-1. Overexpression of c-Jun approximately Fra-1 dimers in primary murine fibroblast cells led to the upregulation of the endogenous ARF protein and growth arrest. Conversely, inhibition of c-Jun or Fra-1 protein levels resulted in decreased ARF expression. In addition, we show that AP-1 dimers cooperate with oncogenic Ras in the transcriptional activation of the p14/p19ARF promoter. Thus, AP-1 heterodimers may contribute to the regulation of ARF expression upon oncogenic signaling.
- Published
- 2005
- Full Text
- View/download PDF