This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jung, D.-J. Articles by Lee, Y. C. Search for Related Content PubMed PubMed Citation Articles by Jung, D.-J. Articles by Lee, Y. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2002, p. 5203-5211, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5203-5211.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Novel Transcription Coactivator Complex Containing Activating Signal Cointegrator 1

Department of Life Science, Pohang University of Science and Technology, Pohang 790-784,¹ Hormone Research Center,² College of Pharmacy, Chonnam National University, Kwangju 500-757, Korea,³ Gene Expression Laboratory, Salk Institute of Biological Sciences, San Diego, California 92037⁴

Received 27 February 2002/ Accepted 14 March 2002

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 B (NF-B) 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-B. 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-B, 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 P50KH, 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-B transactivation and to mediate the transrepression between nuclear receptors and either AP-1 or NF-B in vivo.

This article has been cited by other articles:

• Iyer, L. M., Burroughs, A. M., Aravind, L. (2006). The ASCH superfamily: novel domains with a fold related to the PUA domain and a potential role in RNA metabolism. Bioinformatics 22: 257-263 [Abstract] [Full Text]  
• Auboeuf, D., Dowhan, D. H., Dutertre, M., Martin, N., Berget, S. M., O'Malley, B. W. (2005). A Subset of Nuclear Receptor Coregulators Act as Coupling Proteins during Synthesis and Maturation of RNA Transcripts. Mol. Cell. Biol. 25: 5307-5316 [Full Text]  
• Auboeuf, D., Dowhan, D. H., Kang, Y. K., Larkin, K., Lee, J. W., Berget, S. M., O'Malley, B. W. (2004). Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. Proc. Natl. Acad. Sci. USA 101: 2270-2274 [Abstract] [Full Text]  
• Munz, C., Psichari, E., Mandilis, D., Lavigne, A.-C., Spiliotaki, M., Oehler, T., Davidson, I., Tora, L., Angel, P., Pintzas, A. (2003). TAF7 (TAFII55) Plays a Role in the Transcription Activation by c-Jun. J. Biol. Chem. 278: 21510-21516 [Abstract] [Full Text]  
• Mazumder, R., Iyer, L. M., Vasudevan, S., Aravind, L. (2002). Detection of novel members, structure-function analysis and evolutionary classification of the 2H phosphoesterase superfamily. Nucleic Acids Res 30: 5229-5243 [Abstract] [Full Text]