Cited by 44Cell death mechanisms and regulationCancer-related Molecular PathwaysNF-κB Signaling Pathways

Ligand stimulation of CD95 induces activation of Plk3 followed by phosphorylation of caspase-8

Open access
Helmke, Christina, Raab, Monika, Rödel, Franz, Matthess, Yves, Oellerich, Thomas, Mandal, Ranadip, Sanhaji, Mourad, Urlaub, Henning +3 more·2016·Cell Research

Abstract

Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation. Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. Stimulation of CD95 in cells expressing a non-phosphorylatable caspase-8-T273A mutant in a rescue experiment or in Plk3-KO cells generated by CRISPR/Cas9 reduces the processing of caspase-8 prominently. Low T273 phosphorylation correlates significantly with low Plk3 expression in a cohort of 95 anal tumor patients. Our data suggest a novel mechanism of kinase activation within the Plk family and propose a new model for the stimulation of the extrinsic death pathway in tumors with high Plk3 expression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/cr.2016.78

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Smith MR, Wilson ML, Hamanaka R, et al. Malignant trans- formation of mammalian cells initiated by constitutive expres- sion of the polo-like kinase. Biochem Biophys Res Commun 1997; 234:397-405.

Cited by

Sorted by citations

Authors
Helmke, C., Raab, M., Rödel, F., Matthess, Y., Oellerich, T., Mandal, R., Sanhaji, M., Urlaub, H., Rödel, C., Becker, S., & Strebhardt, K.
Affiliations
  • Goethe University Frankfurt (DE)
  • Universitätsmedizin Göttingen (DE)
Corresponding author
Strebhardt, Klaus
Venue
Cell Research
Published
2016-06-21
Volume
26
Issue
8
Pages
914-934
ISSN
  • 1001-0602 (ISSN-L)
  • 1748-7838
OpenAlex
W2462979737
Cited by
44
References
70
Citations by year
2026: 1 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 2
FWCI
3.29
Type
journal article
Language
en
Open access
Locations
  • Cell Research (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (acceptedVersion, other-oa)
  • GRO (submittedVersion, cc-by-nc-nd)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
  • MPG.PuRe (Max Planck Society) (submittedVersion, cc-by-nc-nd)
Funders
  • Wilhelm Sander-Stiftung
  • Deutsche Krebshilfe
  • Deutschen Konsortium für Translationale Krebsforschung
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
Fas, FADD, PLK3, caspase-8, death-inducing signaling complex, extrinsic apoptotic pathway, death receptor signaling, anal cancer, cancer therapy targets
MeSH terms
Polo-like Kinases, Enzyme Activation, HeLa Cells, Humans, Isotope Labeling, Ligands, Phosphorylation, Phosphothreonine, Protein Binding, Protein Serine-Threonine Kinases, fas Receptor, Jurkat Cells, Tumor Suppressor Proteins, Protein Interaction Mapping, Immunoprecipitation, Caspase 8, Fas-Associated Death Domain Protein, Death Domain Receptor Signaling Adaptor Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review