Mechanism of action of a dominant negative c-jun mutant in inhibiting activator protein-1 activation
| Autor: | Ashok Kumar Gupta, G. Tim Bowden, Eric J. Thompson, M. Suzanne Stratton |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Proto-Oncogene Proteins c-jun Response element CREB Cell Line Mice chemistry.chemical_compound Transactivation stomatognathic system Transcription (biology) medicine Animals skin and connective tissue diseases Molecular Biology Transcription factor DNA Primers Genes Dominant Base Sequence biology c-jun Okadaic acid Precipitin Tests Molecular biology Transcription Factor AP-1 Mechanism of action chemistry Mutation biology.protein medicine.symptom hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Carcinogenesis. 35:157-162 |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.10090 |
| Popis: | The dominant negative c-jun TAM-67 has been shown to inhibit tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate and okadaic acid (OA). To better understand this phenomenon, we investigated the mechanism of action of TAM-67 in response to OA. To identify the mechanism of action, we used a 6xHis-tagged TAM-67 as well as chimeric constructs of TAM-67 that either cannot bind DNA or cannot heterodimerize with wild-type transcription factors. The results of these studies indicated that TAM-67 acts by blocking or squelching. The results of elecrophoretic mobility-shift assays showed that TAM-67 must act by squelching in response to OA, as TAM-67 cannot be found in DNA-binding complexes. We then identified some of the proteins with which TAM-67 interacts. They include all members of the jun and fos families as well as the cAMP response element binding protein, activating transcription factor-1, activating transcription factor-2, and RelA (p65). Thus, we have shown that TAM-67 squelches the induction of activating transcription factor-1 transactivation in response to OA and that TAM-67 is capable of interacting with proteins that control transactivation by binding to the 12-O-tetradecanoylphorbol-13-acetate response element, cAMP response element and nuclear factor-kappaB sites. |
| Databáze: | OpenAIRE |
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