Activating protein-1, nuclear factor-κB, and serum response factor as novel target molecules of the cancer-amplified transcription coactivator ASC-2

Soo Kyung Lee, Soon Young Na, Sung Yun Jung, Ji Eun Choi, Byung Hak Jhun, Jae Hun Cheong, Paul S. Meltzer, Young Chul Lee, Jae Woon Lee

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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-κB (NFκB) 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 NFκB 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 NFκB. Overall, these results suggest that the nuclear receptor coactivator ASC-2 also mediates transactivations by SRF, AP-1, and NFκB, which may contribute to the putative, ASC-2-mediated tumorigenesis.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalMolecular Endocrinology
Volume14
Issue number6
DOIs
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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