Induction of a secreted protein by the myxoid liposarcoma oncogene
| Autor: | David Ron, Yin Yin, Jo Ann W Giannotti, Kenneth A. Jacobs, Katherine J. Turner, Xiaozhong Wang, Patricia Murtha-Riel, Peter Chung, John Sok, Lori Fitz, Masahiko Kuroda |
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| Rok vydání: | 1999 |
| Předmět: |
genetic structures
Oncogene Proteins Fusion Molecular Sequence Data Biology DNA-binding protein Mice hemic and lymphatic diseases medicine Animals Humans Cloning Molecular Nuclear protein Transcription factor Cells Cultured Transcription Factor CHOP Myxoid liposarcoma Multidisciplinary Oncogene Ccaat-enhancer-binding proteins Nuclear Proteins Fibroblasts Biological Sciences medicine.disease Molecular biology Liposarcoma Myxoid Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic CCAAT-Enhancer-Binding Proteins RNA-Binding Protein FUS |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:5025-5030 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.96.9.5025 |
| Popis: | The TLS-CHOP oncoprotein, found in the majority of human myxoid liposarcomas, consists of a fusion between the transcription factor CHOP/GADD153 and the N terminus of an RNA-binding protein TLS/FUS. Clinical correlation and in vitro transformation assays indicate that the N terminus of TLS plays an important role in oncogenesis by TLS-CHOP. Until now, however, the only activity attributed to the oncoprotein is that of inhibiting the binding of transcription factors of the C/EBP class to certain adipogenic target genes, a function that TLS-CHOP shares with the nononcogenic CHOP protein. Here we report the isolation of a gene, DOL54, that is activated in primary fibroblasts by the expression of TLS-CHOP. DOL54 is expressed in the neoplastic component of human myxoid liposarcomas and increases the tumorigenicity of cells injected in nude mice. Activation of DOL54 requires an intact DNA-binding and dimerization domain in TLS-CHOP, a suitable cellular dimerization partner, and depends on the TLS N terminus. Normal adipocytic differentiation is associated with an early and transient expression of DOL54, and the gene encodes a secreted protein that is tightly associated with the cell surface or extracellular matrix. TLS-CHOP thus leads to the unscheduled expression of a gene that is normally associated with adipocytic differentiation. |
| Databáze: | OpenAIRE |
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