Cellular Targets for Activation by c-Myc Include the DNA Metabolism Enzyme Thymidine Kinase
| Autor: | Elke Hengstschläger-Ottnad, Markus Hengstschläger, Gerhard Bernaschek, Thomas Soucek, Oliver Pusch |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cell Cycle Proteins
Biology Thymidine Kinase Cell Line Proto-Oncogene Proteins c-myc Downregulation and upregulation Genetics Animals RNA Messenger Promoter Regions Genetic Molecular Biology Gene Cyclin-Dependent Kinase Inhibitor p16 chemistry.chemical_classification Cell growth Kinase Cell Biology General Medicine Cell cycle Molecular biology Enzyme assay E2F Transcription Factors Rats Up-Regulation DNA-Binding Proteins Enzyme Activation Enzyme chemistry Thymidine kinase biology.protein Carrier Proteins Transcription Factor DP1 Cell Division Retinoblastoma-Binding Protein 1 Transcription Factors |
| Zdroj: | DNA and Cell Biology. 16:737-747 |
| ISSN: | 1557-7430 1044-5498 |
| Popis: | Although a remarkable number of genes has been identified that are either activated or repressed via c-Myc, only few of them obviously contribute to Myc's biological effect--the induction of proliferation. We found that in logarithmically growing cells overexpression of Myc specifically induces thymidine kinase (TK) mRNA expression and enzyme activity, whereas loss of one allele of Myc causes downregulation of this enzyme. We show that activation of Myc triggers high levels of this normally strictly S-phase-regulated DNA metabolism enzyme in serum arrested G0 cells and causes high and constant levels of TK expression throughout the entire ongoing cell cycle. Induction of TK by Myc requires an intact transcriptional activation domain. Myc-induced deregulation of this enzyme is paralleled by alterations of protein binding at the E2F-site of the TK promoter. We further show that cell growth arrest by the cyclin-dependent kinase inhibitor p16 is abrogated by overexpression of Myc and that co-overexpression of p16 cannot inhibit the Myc-induced up-regulation of TK expression. Our data demonstrate TK to be a cellular target of Myc independently of the status of cell proliferation and provide evidence that the transcription factor E2F might be involved in this process. |
| Databáze: | OpenAIRE |
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