Novel Transcription Coactivator Complex Containing Activating Signal Cointegrator 1
| Autor: | Hyun Mi Lee, Janghoo Lim, Young Wha Goo, Tae Sung Kim, Han Jong Kim, Hee Sook Sung, Young Chul Lee, Jae Woon Lee, Soo Kyung Lee, Dong Ju Jung, Ok Ku Park, Sung Yun Jung |
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| Rok vydání: | 2002 |
| Předmět: |
Transcriptional Activation
Serum Response Factor Macromolecular Substances Recombinant Fusion Proteins Molecular Sequence Data Endogeny Biology Transactivation Neutralization Tests Serum response factor Animals Humans ACTIVATING SIGNAL COINTEGRATOR 1 Amino Acid Sequence Molecular Biology Transrepression Cell Nucleus Transcriptional Regulation NF-kappa B Cell Biology Molecular biology Transcription Factor AP-1 Phenotype Nuclear receptor Transcription Coactivator Mutation Ectopic expression HeLa Cells Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 22:5203-5211 |
| ISSN: | 1098-5549 |
| Popis: | Human activating signal cointegrator 1 (hASC-1) was originally isolated as a transcriptional coactivator of nuclear receptors. Here we report that ASC-1 exists as a steady-state complex associated with three polypeptides, P200, P100, and P50, in HeLa nuclei; stimulates transactivation by serum response factor (SRF), activating protein 1 (AP-1), and nuclear factor kappaB (NF-kappaB) through direct binding to SRF, c-Jun, p50, and p65; and relieves the previously described transrepression between nuclear receptors and either AP-1 or NF-kappaB. Interestingly, ectopic expression of Caenorhabditis elegans ASC-1 (ceASC-1), an ASC-1 homologue that binds P200 and P100, like hASC-1, while weakly interacting only with p65, in HeLa cells appears to replace endogenous hASC-1 from the hASC-1 complex and exerts potent dominant-negative effects on AP-1, NF-kappaB, and SRF transactivation. In addition, neutralization of endogenous P50 by single-cell microinjection of a P50 antibody inhibits AP-1 transactivation; the inhibition is relieved by coexpression of wild-type P50, but not of P50DeltaKH, a mutant form that does not interact with P200. Overall, these results suggest that the endogenous hASC-1 complex appears to play an essential role in AP-1, SRF, and NF-kappaB transactivation and to mediate the transrepression between nuclear receptors and either AP-1 or NF-kappaB in vivo. |
| Databáze: | OpenAIRE |
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