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.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Nucleus / metabolism
  • HeLa Cells
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutation
  • NF-kappa B / metabolism
  • Neutralization Tests
  • Phenotype
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serum Response Factor / metabolism
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • Macromolecular Substances
  • NF-kappa B
  • Recombinant Fusion Proteins
  • Serum Response Factor
  • TRIP4 protein, human
  • Transcription Factor AP-1
  • Transcription Factors
  • Trip4 protein, mouse

Associated data

  • GENBANK/AF197574
  • GENBANK/AF197575
  • GENBANK/AY013288
  • GENBANK/AY013289
  • GENBANK/AY013290