Activating protein-1, nuclear factor-kappa B, and serum response factor asnovel target molecules of the cancer-amplified transcription coactivator ASC-2

ASC-2 was recently discovered as a cancer-amplified transcription coactivat or molecule of nuclear receptors, which interacts with multifunctional tran scription integrators steroid receptor coactivator-1 (SRC-1) and CREB-bindi ng protein (CBP)/p300. Herein, we report the identification of three mitoge nic transcription factors as novel target molecules of ASC-2. First, the C- terminal transactivation domain of serum response factor (SRF) was identifi ed among a series of ASC-2-interacting proteins from the yeast two-hybrid s creening. Second, ASC-2 specifically interacted with the activating protein -1 (AP-1) components c-Jun and c-Fos as well as the nuclear factor-kappa B (NF kappa B) components p50 and p65, as demonstrated by the glutathione S-t ransferase pull-down assays as well as the yeast two-hybrid tests. In cotra nsfection of mammalian cells, ASC-2 potentiated transactivations by SRF, AP -1, and NF kappa B in a dose-dependent manner, either alone or in conjuncti on with SRC-1 and p300. In addition, ASC-2 efficiently relieved the previou sly described transrepression between nuclear receptors and either AP-1 or NF kappa B. Overall, these results suggest that the nuclear receptor coacti vator ASC-2 also mediates transactivations by SRF, AP-1, and NF kappa B, wh ich may contribute to the putative, ASC-2-mediated tumorigenesis.