Intracellular interleukin-1alpha functionally interacts with histone acetyltransferase complexes

Miroslava Buryskova1, Martin Pospisek, Arnhild Grothey

  • 1Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, D-89081 Ulm, Germany.

Insights

Interleukin-1alpha (IL-1alpha), a cytokine, translocates into the nucleus. This study reveals IL-1alpha

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Interleukin-1alpha (IL-1alpha) is primarily known as an extracellular inflammatory cytokine.
  • A portion of synthesized IL-1alpha is translocated into the cell nucleus, suggesting intracellular functions.
  • The precise mechanisms of IL-1alpha's intracellular roles in proliferation, apoptosis, and migration remain unknown.

Purpose of the Study:

  • To investigate the nuclear functions of intracellular Interleukin-1alpha.
  • To elucidate the molecular mechanisms underlying IL-1alpha's nuclear activities.
  • To identify nuclear targets and interacting partners of IL-1alpha.

Main Methods:

  • Fusion of intracellular IL-1alpha to the Gal4 DNA-binding domain (Gal4BD) to assess transactivation potential.
  • Co-expression with transcriptional coactivator p300 to evaluate synergistic effects.
  • Interaction studies using yeast strains to identify binding partners and analyze phenotypes.
  • Investigating the role of the IL-1alpha N-terminal peptide (IL-1NTP) in complex formation.

Main Results:

  • Intracellular IL-1alpha fused to Gal4BD exhibits significant transactivation potential, enhanced by p300.
  • The IL-1alpha precursor interacts with histone acetyltransferases (p300, PCAF, Gcn5) and Ada3 via its N-terminal peptide (IL-1NTP).
  • IL-1NTP integrates into the PCAF.p300 complex without disruption.
  • Expression of Gal4BD/IL-1NTP induces a toxic phenotype in yeast, which is alleviated by depleting SAGA complex components.

Conclusions:

  • Provides the first evidence for the nuclear target of the IL-1alpha precursor.
  • Suggests a novel function for intracellular IL-1alpha in transcriptional control.
  • Highlights the interaction of IL-1alpha with histone acetyltransferases and its integration into transcriptional regulatory complexes.

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