Activating protein-1, nuclear factor-kappaB, and serum response factor as novel target molecules of the

S K Lee1, S Y Na, S Y Jung

  • 1Center for Ligand and Transcription, Department of Biology, Chonnam National University, Kwangju, Korea.

Insights

The cancer-associated coactivator ASC-2 interacts with transcription factors serum response factor (SRF), activating protein-1 (AP-1), and nuclear factor-kappaB (NFkappaB). ASC-2 enhances their activity and may play a role in tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Gene Regulation

Background:

  • ASC-2 (Amplifier of the Splicing Complex 2) is a known coactivator for nuclear receptors involved in cancer.
  • It interacts with other coactivators like SRC-1 and CBP/p300.
  • The full range of ASC-2's interactions and functions in gene regulation is not completely understood.

Purpose of the Study:

  • To identify novel target molecules of the coactivator ASC-2.
  • To investigate the interaction of ASC-2 with specific transcription factors.
  • To determine the functional consequences of ASC-2's interactions on gene transactivation and its role in tumorigenesis.

Main Methods:

  • Yeast two-hybrid screening to identify ASC-2 interacting proteins.
  • Glutathione S-transferase (GST) pull-down assays to confirm interactions.
  • Mammalian cell cotransfection assays to assess effects on gene transactivation.

Main Results:

  • ASC-2 directly interacts with serum response factor (SRF), c-Jun/c-Fos (AP-1), and p50/p65 (NFkappaB).
  • ASC-2 potentiates the transactivation activity of SRF, AP-1, and NFkappaB in a dose-dependent manner.
  • ASC-2 alleviates transrepression between nuclear receptors and AP-1 or NFkappaB.

Conclusions:

  • ASC-2 functions not only as a nuclear receptor coactivator but also mediates transactivation by SRF, AP-1, and NFkappaB.
  • These newly identified interactions suggest a broader role for ASC-2 in gene regulation.
  • ASC-2's involvement in the activation of these transcription factors may contribute to cancer development.

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