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Pervasive phenotypic effects of FBXO42 are promoted by regulation of PP4 phosphatase

Hongbin Yang1, Paul Smith2, Yingying Ma3

  • 1Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Singapore.

The EMBO Journal
|January 4, 2026
PubMed

Insights

FBXO42 regulates the protein phosphatase PP4 by ubiquitination, controlling its activity. This finding reveals FBXO42 as a key player in ubiquitin signaling with potential therapeutic applications.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • F-box proteins are crucial components of the SCF E3 ubiquitin ligase complex.
  • FBXO42 is an understudied F-box protein involved in cell cycle, DNA damage response, and glioma stem cell survival.

Purpose of the Study:

  • To elucidate the function of FBXO42 in regulating protein phosphatase PP4.
  • To understand the mechanism by which FBXO42 controls PP4 activity.

Main Methods:

  • Investigated the interaction between FBXO42 and the PP4 complex.
  • Analyzed the ubiquitination of PP4 subunits by FBXO42.
  • Assessed the impact of FBXO42 on PP4 phosphatase activity.

Main Results:

  • FBXO42 directly ubiquitinates the PP4 complex, regulating subunit assembly.
  • FBXO42 restrains the catalytic activity of PP4.
  • Depletion of FBXO42 leads to increased PP4 activity and significant cellular effects.

Conclusions:

  • FBXO42 is a major regulator of protein phosphatase PP4 activity.
  • FBXO42 acts as a novel regulatory node in ubiquitin-mediated signaling.
  • FBXO42 represents a potential target for therapeutic exploitation.
Keywords:
CRLsF-box ProteinsFBXO42PP4 PhosphataseUbiquitin

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