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

Author information

Affiliations

  • 1. Center 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.
      Authors
    • Iliaki S 1
    • Kreike M 1
    • De Meyer F 1
    • Aidarova A 1
    • Braun H 1
    • Afonina IS 1
    • Beyaert R 1
    (7 authors)
  • 2. Center 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; Center for Inflammation Research, Unit of Mouse Genetics and Inflammation, VIB, B-9052 Ghent, Belgium.
      Authors
    • Ferreras Moreno N 2
    (1 author)
  • 3. Department of Biomedical Molecular Biology, Ghent University, B-9052 Ghent, Belgium; Center for Inflammation Research, Unit of Mouse Genetics and Inflammation, VIB, B-9052 Ghent, Belgium.
      Authors
    • Libert C 3
    (1 author)

ORCIDs linked to this article

Biochemical Pharmacology, 24 May 2024, 228:116316
https://doi.org/10.1016/j.bcp.2024.116316 PMID: 38797267 

Abstract 

Caspase recruitment domain (CARD)-containing protein 14 (CARD14) is an intracellular protein that mediates nuclear factor-kappa B (NF-ĸB) signaling and proinflammatory gene expression in skin keratinocytes. Several hyperactivating CARD14 mutations have been associated with psoriasis and other inflammatory skin diseases. CARD14-induced NF-ĸB signaling is dependent on the formation of a CARD14-BCL10-MALT1 (CBM) signaling complex, but upstream receptors and molecular mechanisms that activate and regulate CARD14 signaling are still largely unclear. Using unbiased affinity purification and mass spectrometry (AP-MS) screening, we discover polo-like kinase 1 (PLK1) as a novel CARD14-binding protein. CARD14-PLK1 binding is independent of the CARD14 CARD domain but involves a consensus phospho-dependent PLK1-binding motif in the CARD14 linker region (LR). Expression of the psoriasis-associated CARD14(E138A) variant in human keratinocytes induces the recruitment of PLK1 to CARD14-containing signalosomes in interphase cells, but does not affect the specific location of PLK1 in mitotic cells. Finally, disruption of the PLK1-binding motif in CARD14(E138A) increases CARD14-induced proinflammatory signaling and gene expression. Together, our data identify PLK1 as a novel CARD14-binding protein and indicate a negative regulatory role for PLK1 in CARD14 signaling.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.bcp.2024.116316

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Funding 

Funders who supported this work.

FWO

    Foundation Against Cancer

      Ghent University

        National Psoriasis Foundation