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Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1

Ralf Janknecht1

  • 1Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA. janknecht.ralf@mayo.edu

Oncogene
|February 6, 2003
PubMed

Insights

Mitogen- and stress-activated protein kinase 1 (MSK1) regulates the transcription factor ER81. MSK1 directly phosphorylates ER81 and stimulates coactivators, impacting ER81 function in development and breast cancer.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • The transcription factor ER81 plays a role in development and breast tumor formation.
  • ER81 activity is regulated by phosphorylation, often mediated by mitogen-activated protein kinases (MAPKs).
  • The specific protein kinases regulating ER81 have not been fully elucidated.

Purpose of the Study:

  • To identify and characterize the protein kinase(s) that regulate ER81 function.
  • To investigate the role of mitogen- and stress-activated protein kinase 1 (MSK1) in ER81-dependent transcription.
  • To elucidate the mechanisms by which MSK1 influences ER81 activity.

Main Methods:

  • MSK1 expression and its effect on ER81-dependent transcription were analyzed.
  • Site-directed mutagenesis was used to identify MSK1 phosphorylation sites on ER81.
  • Co-immunoprecipitation assays were performed to assess interactions between MSK1, ER81, and coactivators CBP/p300.

Main Results:

  • MSK1 enhances ER81-dependent transcription, particularly upon p38-MAPK pathway stimulation.
  • MSK1 directly phosphorylates ER81 at two specific serine residues, which are critical for MSK1-mediated stimulation.
  • MSK1 also interacts with and stimulates the coactivators CBP and p300, suggesting a dual mechanism of action.

Conclusions:

  • MSK1 is a key regulator of ER81 function.
  • MSK1 regulates ER81 through direct phosphorylation and by enhancing the activity of coactivators CBP/p300.
  • These findings provide insights into ER81 regulation in normal development and mammary tumor formation.

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