title: Novel transcription coactivator complex containing activating signal cointegrator 1.
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.
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Jung
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Sung
authors.forename: Young-Wha
authors.initials: YW
authors.lastname: Goo
authors.forename: Hyun Mi
authors.initials: HM
authors.lastname: Lee
authors.forename: Ok Ku
authors.initials: OK
authors.lastname: Park
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Janghoo
authors.initials: J
authors.lastname: Lim
authors.forename: Han-Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.forename: Jae Woon
authors.initials: JW
authors.lastname: Lee
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D009500:Neutralization Tests; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D046911:Macromolecular Substances; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D026362:Serum Response Factor; C459901:TRIP4 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C459902:Trip4 protein, mouse