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Functional interaction of protein kinase CK2 and activating transcription factor 4 (ATF4), a key player in the

Emmanuel Ampofo1, Tasja Sokolowsky, Claudia Götz

  • 1Medizinische Biochemie und Molekularbiologie und Kompetenzzentrum, Molekulare Medizin, Universität des Saarlandes, Gebäude 44, 66424 Homburg, Germany.

Biochimica Et Biophysica Acta
|November 6, 2012
PubMed

Insights

Protein kinase CK2 regulates ER stress signaling by phosphorylating activating transcription factor 4 (ATF4). This phosphorylation affects ATF4 stability, gene transcription, and its activity as a transcription factor.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Biochemistry

Background:

  • Protein kinase CK2 is a key regulator of diverse biological processes.
  • CK2 exerts its functions through protein binding and substrate phosphorylation.
  • Activating transcription factor 4 (ATF4) is crucial for the endoplasmic reticulum (ER) stress response.

Purpose of the Study:

  • To identify new binding partners and substrates of CK2.
  • To investigate the role of CK2 in regulating ATF4 function and ER stress signaling.

Main Methods:

  • Bifluorescence complementation analysis (BiFC) to detect protein interactions.
  • Site-directed mutagenesis to identify phosphorylation sites.
  • In vitro and in vivo assays to assess protein stability, gene transcription, and transcription factor activity.

Main Results:

  • ATF4 was identified as a novel binding partner and substrate of CK2.
  • Serine 215 (S215) was identified as the primary CK2 phosphorylation site on ATF4.
  • CK2 phosphorylation of ATF4 impacts its stability, transcriptional regulation, and overall activity.
  • CK2 inhibition led to increased ATF4 gene transcription.

Conclusions:

  • CK2 directly regulates ATF4, a key player in ER stress.
  • CK2 phosphorylation of ATF4 influences its stability and transcriptional activity.
  • CK2 plays a critical role in modulating the ER stress signaling pathway through ATF4.

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