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Integrin-linked kinase regulates the nuclear entry of the c-Jun coactivator alpha-NAC and its coactivation potency

Isabelle Quélo1, Claude Gauthier, Gregory E Hannigan

  • 1Genetics Unit, Shriners Hospital for Children Montréal, Québec H3G 1A6, Canada.

The Journal of Biological Chemistry
|August 10, 2004
PubMed

Insights

Integrin-linked kinase (ILK) enhances c-Jun transcription by phosphorylating the coactivator alpha-NAC. This phosphorylation drives alpha-NAC nuclear accumulation, a key step for ILK

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Integrin-linked kinase (ILK) is known to regulate gene transcription.
  • c-Jun is a transcription factor involved in various cellular processes.
  • Transcriptional coactivators play crucial roles in modulating gene expression.

Purpose of the Study:

  • To elucidate the mechanism by which ILK enhances c-Jun-dependent transcription.
  • To investigate the role of the coactivator nascent polypeptide-associated complex and coactivator alpha (alpha-NAC) in ILK-mediated transcriptional regulation.
  • To determine if ILK-dependent phosphorylation of alpha-NAC is essential for its function.

Main Methods:

  • Cell adhesion assays using fibronectin.
  • Co-expression of wild-type and mutant forms of ILK and alpha-NAC.
  • Analysis of alpha-NAC localization (cytoplasmic vs. nuclear) using cell imaging.
  • Assessment of c-Jun-dependent transcriptional activity.

Main Results:

  • ILK phosphorylates alpha-NAC at Ser-43 upon cell adhesion to fibronectin.
  • Active ILK promotes nuclear accumulation of alpha-NAC, while dominant-negative ILK or S43A alpha-NAC mutant prevents it.
  • The S43A alpha-NAC mutant fails to potentiate ILK's effect on c-Jun transcription.

Conclusions:

  • ILK-dependent phosphorylation of alpha-NAC is critical for its nuclear translocation.
  • Phosphorylation of alpha-NAC by ILK is required for enhancing c-Jun-mediated responses.
  • This study demonstrates a novel mechanism of coactivator regulation involving ILK-mediated phosphorylation and nucleocytoplasmic shuttling.

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