Activating Protein-1, Nuclear Factor-κB, and Serum Response Factor as Novel Target Molecules of the Cancer-Amplified Transcription Coactivator ASC-2
| Autor: | Paul S. Meltzer, Sung Yun Jung, Ji-Eun Choi, Byung Hak Jhun, Soo Kyung Lee, Jae Hun Cheong, Jae Woon Lee, Young Chul Lee, Soon Young Na |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Transcriptional Activation
Serum Response Factor Recombinant Fusion Proteins Nuclear Receptor Coactivators Gene Expression Transfection Mice Transactivation Endocrinology Genes jun Transcription (biology) Neoplasms Serum response factor Animals Humans Molecular Biology Transcription factor Glutathione Transferase Binding Sites biology Intracellular Signaling Peptides and Proteins NF-kappa B Genes fos Nuclear Proteins Drug Synergism 3T3 Cells DNA General Medicine Molecular biology eye diseases Activating transcription factor 2 DNA-Binding Proteins Transcription Factor AP-1 Nuclear receptor Transcription Coactivator Nuclear receptor coactivator 3 biology.protein tissues HeLa Cells Transcription Factors |
| Zdroj: | Molecular Endocrinology. 14:915-925 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/mend.14.6.0471 |
| Popis: | ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappaB (NFkappaB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFkappaB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFkappaB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFkappaB, which may contribute to the putative, ASC-2-mediated tumorigenesis. |
| Databáze: | OpenAIRE |
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