KRAB-independent suppression of neoplastic cell growth by the novel zinc finger transcription factor KS1
| Autor: | Brian Gebelein, Martin E. Fernandez-Zapico, Mami Imoto, Raul Urrutia |
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| Rok vydání: | 1998 |
| Předmět: |
Genes
Wilms Tumor Transcription Genetic Protein Conformation Molecular Sequence Data Kruppel-Like Transcription Factors Biology Mice Tumor Cells Cultured Animals Genes Tumor Suppressor Neoplastic transformation Amino Acid Sequence Pancreas Gene Library Cell Nucleus Zinc finger transcription factor Zinc finger Sp1 transcription factor Base Sequence Epidermal Growth Factor Sequence Homology Amino Acid C2H2 Zinc Finger GATA4 Nuclear Proteins Zinc Fingers 3T3 Cells General Medicine Zinc finger nuclease Molecular biology Neoplasm Proteins Rats DNA-Binding Proteins Pancreatic Neoplasms Repressor Proteins RING finger domain Cell Transformation Neoplastic Genes ras Gene Expression Regulation Genes Multigene Family Sequence Alignment Research Article Transcription Factors |
| Zdroj: | Journal of Clinical Investigation. 102:1911-1919 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci1919 |
| Popis: | The study of zinc finger proteins has revealed their potential to act as oncogenes or tumor suppressors. Here we report the molecular, biochemical, and functional characterization of KS1 (KRAB/zinc finger suppressor protein 1), a novel, ubiquitously expressed zinc finger gene initially isolated from a rat pancreas library. KS1 contains 10 C2H2 zinc fingers, a KRAB-A/B motif, and an ID sequence that has been shown previously to participate in growth factor-regulated gene expression. Northern blot analysis using pancreatic cell lines demonstrates that KS1 mRNA is inducible by serum and epidermal growth factor, suggesting a role for this gene in cell growth regulation. Biochemical analysis reveals that KS1 is a nuclear protein containing two transcriptional repressor domains, R1 and R2. R1 corresponds to the KRAB-A motif, whereas R2 represents a novel sequence. Transformation assays using NIH3T3 cells demonstrate that KS1 suppresses transformation by the potent oncogenes Ha-ras, Galpha12, and Galpha13. Deletion of the R1/ KRAB-A domain does not modify the transformation suppressive activity of KS1, whereas deletion of R2 abolishes this function. Thus, KS1 is a novel growth factor-inducible zinc finger transcriptional repressor protein with the potential to protect against neoplastic transformation induced by several oncogenes. |
| Databáze: | OpenAIRE |
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