Related Experiment Video

Updated: Jul 16, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

The regulation of protein phosphatase 4 by FBXO42 is required for cancer cell survival

Stephan H Spangenberg1,2, Nicholas Garaffo3,4, Enya Marie Catherine Alcindor1,2

  • 1Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.

EMBO Reports
|July 14, 2026
PubMed

Insights

FBXO42 and CCDC6 independently regulate protein phosphatase 4 (PPP4C). Aberrant PPP4C activation drives cell death when FBXO42 or CCDC6 is compromised, revealing their distinct roles in cancer cell viability.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • FBXO42 is an F-box protein crucial for numerous cancer cell lines.
  • FBXO42's functional correlation with CCDC6 suggests a shared pathway, but their precise relationship is unclear.

Purpose of the Study:

  • To elucidate the functional relationship between FBXO42, CCDC6, and protein phosphatase 4 (PPP4C).
  • To understand the distinct mechanisms by which FBXO42 and CCDC6 regulate PPP4C.

Main Methods:

  • Co-immunoprecipitation assays to confirm protein interactions.
  • Ubiquitination assays to assess FBXO42's effect on PPP4C.
  • siRNA-mediated knockdown to evaluate cellular viability.

Main Results:

  • FBXO42 directly ubiquitinates and negatively regulates PPP4C.
  • FBXO42 and CCDC6 bind to PPP4C independently, indicating separate regulatory mechanisms.
  • Knockdown of PPP4C rescues cell viability in FBXO42/CCDC6-dependent glioblastoma cells.

Conclusions:

  • FBXO42 and CCDC6 independently regulate PPP4C through distinct mechanisms.
  • Aberrant PPP4C activation contributes to cell death when FBXO42 or CCDC6 function is impaired.
  • These findings provide mechanistic insight into the FBXO42-CCDC6-PPP4C axis in cancer cell biology.

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