Myristylation-dependent transactivation by FBR v-fos is regulated by C/EBP

• Published in: The Journal of biological chemistry Vol. 269; no. 23; pp. 16383 - 16396
• Main Authors: JOTTE, R. M, KAMATA, N, HOLT, J. T
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 10.06.1994
• Subjects: Adipocytes - physiology; Animals; Base Sequence; Biological and medical sciences; CCAAT-Enhancer-Binding Proteins; Cell Differentiation - genetics; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Cell Transformation, Viral; Collagen - genetics; DNA Mutational Analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; HeLa Cells - metabolism; Humans; Matrix Metalloproteinase 3; Metalloendopeptidases - genetics; Models, Genetic; Molecular and cellular biology; Molecular Sequence Data; Myristates - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oncogene Proteins v-fos - genetics; Oncogene Proteins v-fos - isolation & purification; Oncogene Proteins v-fos - metabolism; Promoter Regions, Genetic - genetics; Protein Binding; Protein Processing, Post-Translational; Sarcoma - metabolism; Transcription, Genetic; Transcriptional Activation; Regulation(control); Myristic acid; Structure activity relation; Transcription; V-Onc gene; Cell transformation; Transcription factor; Transcription factor C/EBP; Acylation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(17)34019-X

Viral oncogenes are generally believed to cause transformation through disregulated mimicry of their cellular homologues. However, here we show that FBR v-fos, unlike c-fos, transcriptionally activates unique genes in retrovirally induced chondro-osseous sarcomas. We show that FBR v-fos transactivates the collagen III and stromelysin promoters and that the unique transcriptional properties of transforming FBR depend upon its N-terminal myristylation and the differentiation state of the cell. Deletion or mutation of the myristylation site results in a loss of FBR v-fos transactivation in HeLa and undifferentiated 3T3-L1 preadipocyte cell lines. FBR v-fos transactivation of collagen III maps to a negative regulatory site which binds a key regulator of adipocyte differentiation, C/EBP alpha. Cotransfection of C/EBP alpha abolishes FBR v-fos transactivation of the alpha 1(III) collagen promoter. Furthermore, FBR v-fos cannot transactivate collagen III subsequent to adipocyte differentiation. We also demonstrate that collagen III transcription is reduced during adipocyte differentiation as the transcriptional activity of C/EBP alpha is concomitantly induced. Our results indicate that FBR v-fos transactivation depends upon its cotranslational myristylation and maps to a negative regulatory region which binds C/EBP alpha.