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

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-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.

• Authors: S K Lee, S Y Na, S Y Jung, J E Choi, B H Jhun, J Cheong, P S Meltzer, Y C Lee, J W Lee
• Journal: Molecular endocrinology (Baltimore, Md.) (Mol Endocrinol) Vol. 14 Issue 6 Pg. 915-25 (Jun 2000) ISSN: 0888-8809 [Print] United States
• PMID: 10847592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Intracellular Signaling Peptides and Proteins
• NCOA6 protein, human
• NF-kappa B
• Ncoa6 protein, mouse
• Nuclear Proteins
• Nuclear Receptor Coactivators
• Recombinant Fusion Proteins
• Serum Response Factor
• Transcription Factor AP-1
• Transcription Factors
• DNA
• Glutathione Transferase

Topics

• 3T3 Cells
• Animals
• Binding Sites
• DNA (metabolism)
• DNA-Binding Proteins (genetics, metabolism, pharmacology)
• Drug Synergism
• Gene Expression
• Genes, fos
• Genes, jun
• Glutathione Transferase (genetics)
• HeLa Cells
• Humans
• Intracellular Signaling Peptides and Proteins
• Mice
• NF-kappa B (genetics, metabolism, pharmacology)
• Neoplasms (metabolism)
• Nuclear Proteins (genetics, metabolism, pharmacology)
• Nuclear Receptor Coactivators
• Recombinant Fusion Proteins (metabolism)
• Serum Response Factor
• Transcription Factor AP-1 (genetics, metabolism, pharmacology)
• Transcription Factors (genetics, metabolism, pharmacology)
• Transcriptional Activation (drug effects)
• Transfection