Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2.
ASC-2 was recently discovered as a cancer-amplified transcription coactivator molecule of nuclear receptors, which interacts with multifunctional transcription integrators steroid receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP)/p300. Herein, we report the identification of three mitogenic transcription factors as novel target molecules of ASC-2. First, the C-terminal transactivation domain of serum response factor (SRF) was identified among a series of ASC-2-interacting proteins from the yeast two-hybrid screening. Second, ASC-2 specifically interacted with the activating protein-1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappaB (NFkappaB) components p50 and p65, as demonstrated by the glutathione S-transferase pull-down assays as well as the yeast two-hybrid tests. In cotransfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP-1, and NFkappaB in a dose-dependent manner, either alone or in conjunction with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previously described transrepression between nuclear receptors and either AP-1 or NFkappaB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFkappaB, which may contribute to the putative, ASC-2-mediated tumorigenesis.
Lee
S K
SK
Center for Ligand and Transcription, Department of Biology, Chonnam National University, Kwangju, Korea.
Na
S Y
SY
Jung
S Y
SY
Choi
J E
JE
Jhun
B H
BH
Cheong
J
J
Meltzer
P S
PS
Lee
Y C
YC
Lee
J W
JW
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D015870:Gene Expression; D016762:Genes, fos; D016758:Genes, jun; D005982:Glutathione Transferase / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D056918:Nuclear Receptor Coactivators; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D026362:Serum Response Factor; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D016328:NF-kappa B; C405683:Ncoa6 protein, mouse; D009687:Nuclear Proteins; D056918:Nuclear Receptor Coactivators; D011993:Recombinant Fusion Proteins; D026362:Serum Response Factor; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA; D005982:Glutathione Transferase