1. Academic Validation
  2. Novel transcription coactivator complex containing activating signal cointegrator 1

Novel transcription coactivator complex containing activating signal cointegrator 1

  • Mol Cell Biol. 2002 Jul;22(14):5203-11. doi: 10.1128/MCB.22.14.5203-5211.2002.
Dong-Ju Jung 1 Hee-Sook Sung Young-Wha Goo Hyun Mi Lee Ok Ku Park Sung-Yun Jung Janghoo Lim Han-Jong Kim Soo-Kyung Lee Tae Sung Kim Jae Woon Lee Young Chul Lee
Affiliations

Affiliation

  • 1 Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
Abstract

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.

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