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Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
11:02

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors

Y Kamei1, L Xu, T Heinzel

  • 1Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, La Jolla, 92093-0648, USA.

Cell
|May 3, 1996
PubMed

Insights

Nuclear receptors require CREB-binding protein (CBP) for activation and inhibit AP-1 through competition for CBP/p300. CBP integrates multiple signaling pathways in the nucleus, acting as a common factor for nuclear receptors, CREB, and AP-1.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • Nuclear receptors are key regulators of gene expression.
  • They activate target genes and inhibit AP-1 activity.
  • The precise mechanisms underlying these functions are complex.

Purpose of the Study:

  • To investigate the role of CREB-binding protein (CBP) in nuclear receptor-mediated gene regulation.
  • To elucidate the mechanism by which nuclear receptors inhibit AP-1 activity.
  • To identify common factors integrating multiple signaling pathways within the nucleus.

Main Methods:

  • Co-immunoprecipitation assays to study protein interactions.
  • Analysis of nuclear receptor and AP-1 activity in cells.
  • Cloning and characterization of nuclear receptor coactivators.

Main Results:

  • Nuclear receptor activation unexpectedly requires CREB-binding protein (CBP).
  • Inhibition of AP-1 activity appears to result from competition for limited CBP/p300.
  • CBP directly interacts with nuclear receptors and p160 coactivators (SRC-1 variants).

Conclusions:

  • CBP is a common factor essential for the function of nuclear receptors, CREB, and AP-1.
  • CBP/p300 acts as an integrator of multiple nuclear signal transduction pathways.
  • Distinct coactivators, like SRC-1 variants, work with CBP for nuclear receptor function.

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