Novel transcription coactivator complex containing activating signal cointegrator 1.
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.
Jung
Dong-Ju
DJ
Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, Korea.
Sung
Hee-Sook
HS
Goo
Young-Wha
YW
Lee
Hyun Mi
HM
Park
Ok Ku
OK
Jung
Sung-Yun
SY
Lim
Janghoo
J
Kim
Han-Jong
HJ
Lee
Soo-Kyung
SK
Kim
Tae Sung
TS
Lee
Jae Woon
JW
Lee
Young Chul
YC
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
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