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A coactivator trap identifies NONO (p54nrb) as a component of the cAMP-signaling pathway

Antonio L Amelio1, Loren J Miraglia, Juliana J Conkright

  • 1Departments of Cancer Biology and Molecular Therapeutics and Translational Research Institute, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, FL 33458, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 14, 2007
PubMed

Insights

A new "coactivator trap" method identified NONO as crucial for cAMP signaling. NONO protein bridges transcription factors and RNA polymerase II, enabling adaptive cellular responses.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Gene Regulation

Background:

  • Signal transduction pathways rely on transcriptional regulation for cellular adaptation.
  • Coactivator proteins are key intermediaries linking transcription factors to the transcriptional machinery.
  • Understanding coactivator-transcription factor interactions is vital for deciphering gene regulation.

Purpose of the Study:

  • To develop and apply a high-throughput screening strategy, the "coactivator trap," for studying coactivator-transcription factor functional interactions.
  • To investigate coactivator involvement in the cAMP signaling pathway, focusing on CBP/p300 and TORC families.
  • To identify novel proteins interacting with coactivators in response to cAMP signaling.

Main Methods:

  • Development of a high-throughput cell-based screening assay, the "coactivator trap."
  • Application of the coactivator trap to the cAMP signaling pathway.
  • Utilized RNA interference (RNAi) to validate the functional role of identified interacting proteins.

Main Results:

  • The coactivator trap successfully identified known and novel coactivator interactions.
  • NONO (p54(nrb)) was identified as a novel interacting protein with the transducers of regulated CREB activity (TORC) family of coactivators.
  • NONO is essential for cAMP-dependent activation of CREB target genes and facilitates complex formation on cAMP-responsive promoters, linking the CREB/TORC complex to RNA polymerase II.

Conclusions:

  • The coactivator trap is an effective strategy for identifying functional coactivator interactions.
  • NONO plays a critical role as a coactivator in cAMP-mediated gene transcription.
  • This study elucidates a novel mechanism in cAMP signal transduction involving NONO as a bridge in the transcriptional complex.

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