Related Experiment Video

Updated: Jun 25, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.6K

Polo-like kinase 1 (PLK1) is a novel CARD14-binding protein in keratinocytes

Styliani Iliaki1, Marja Kreike1, Natalia Ferreras Moreno2

  • 1Center for Inflammation Research, Unit of Molecular Signal Transduction in Inflammation, VIB, B-9052 Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium.

Biochemical Pharmacology
|May 26, 2024
PubMed

Insights

Polo-like kinase 1 (PLK1) binds to CARD14, a protein implicated in inflammatory skin diseases like psoriasis. Disrupting this interaction enhances CARD14 signaling, suggesting PLK1 negatively regulates this pathway.

Area of Science:

  • Immunology
  • Cell Biology
  • Dermatology

Background:

  • Caspase recruitment domain (CARD)-containing protein 14 (CARD14) is crucial for NF-κB signaling and inflammatory gene expression in skin keratinocytes.
  • Hyperactivating CARD14 mutations are linked to inflammatory skin diseases, including psoriasis.
  • The upstream regulation of CARD14 signaling remains poorly understood.

Purpose of the Study:

  • To identify novel CARD14-binding proteins and elucidate their role in regulating CARD14 signaling.
  • To investigate the interaction between CARD14 and polo-like kinase 1 (PLK1).

Main Methods:

  • Unbiased affinity purification coupled with mass spectrometry (AP-MS) was employed to screen for CARD14-binding proteins.
  • The binding interaction between CARD14 and PLK1 was characterized.
  • The functional impact of PLK1 binding on CARD14 signaling was assessed using psoriasis-associated CARD14 variants in human keratinocytes.

Main Results:

  • Polo-like kinase 1 (PLK1) was identified as a novel CARD14-binding protein.
  • CARD14-PLK1 binding occurs via a phospho-dependent motif in the CARD14 linker region and is independent of the CARD14 CARD domain.
  • Disruption of the PLK1-binding motif in a psoriasis-associated CARD14 variant (CARD14(E138A)) led to increased CARD14-induced inflammatory signaling and gene expression.

Conclusions:

  • PLK1 is a novel negative regulator of CARD14-mediated inflammatory signaling.
  • Understanding the CARD14-PLK1 interaction may offer new therapeutic targets for inflammatory skin diseases.

Keywords:
CARD14 signalingMitosisNF-ĸBPLK1PhosphorylationPsoriasis

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