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B, and Serum Response Factor as Novel Target Molecules of the Cancer-Amplified Transcription Coactivator ASC-2
Center for Ligand and Transcription (S.-K.L., S.-Y.N., S.-Y.J., J.H.C., Y.C.L., J.W.L.) Department of Biology (S.-K.L., S.-Y.N.) and Hormone Research Center (J.H.C., Y.C.L., J.W.L.) Chonnam National University Kwangju 500757, Korea College of Pharmacy (J.-E.C., B.H.J.) Pusan National University Pusan 609735, Korea Cancer Genetics Branch (P.S.M.) National Human Genome Research Institute National Institutes of Health Bethesda, Maryland 20892-4470
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-
B (NF
B) 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
NF
B 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
NF
B. Overall, these results suggest that the nuclear receptor
coactivator ASC-2 also mediates transactivations by SRF, AP-1, and
NF
B, which may contribute to the putative, ASC-2-mediated
tumorigenesis.
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