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Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated

R Janknecht1

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

The Journal of Biological Chemistry
|September 12, 2001
PubMed

Insights

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) phosphorylates the ER81 transcription factor, impacting its activity. This interaction, identified as a novel target, may influence tumorigenesis and development.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of gene regulation
  • Signal transduction pathways

Background:

  • Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is a key mediator of cellular stress responses.
  • ETS transcription factors, including ER81, play critical roles in development and are implicated in tumorigenesis when dysregulated.

Purpose of the Study:

  • To identify novel targets of MK2.
  • To investigate the functional consequences of MK2-mediated phosphorylation of ER81.
  • To elucidate the role of MK2 in regulating ER81 transcriptional activity.

Main Methods:

  • In vitro kinase assays to determine MK2 phosphorylation of ER81.
  • Site-directed mutagenesis to identify MK2 phosphorylation sites on ER81.
  • Reporter gene assays to assess ER81-dependent transcription.
  • Overexpression studies in cell culture models.

Main Results:

  • MK2 directly phosphorylates ER81 at serine residues 191 and 216 in vitro and in vivo.
  • MK2 suppresses basal ER81-dependent transcription, an effect partially dependent on phosphorylation.
  • MK2 can inhibit ER81 activity independently of these specific phosphorylation sites.
  • MK2 overexpression counteracts p38 MAPK-stimulated ER81 activity.

Conclusions:

  • MK2 is a novel regulator of the ETS transcription factor ER81.
  • MK2 modulates ER81 transcriptional activity in a cell type-specific manner.
  • This regulation extends beyond stress responses, potentially influencing development and tumorigenesis.

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