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<p>F-box proteins are the substrate recognition modules of the SCF (SKP1–Cullin–F-box) E3 ubiquitin ligase complex. FBXO42, an understudied member of this family, has recently emerged as a modulator of key cellular processes, including cell cycle progression, the&#xa0;DNA damage response, and glioma stem cell survival. In this study, we define the function of FBXO42 as a major regulator of the protein phosphatase PP4. Phosphoprotein phosphatases (PPPs) have a broad array of substrates, hence necessitating tight regulation. We observe that FBXO42 ubiquitinates the PP4 complex to govern the assembly of regulatory and catalytic subunits, with the net effect of restraining the latter’s phosphatase activity. FBXO42 depletion unleashes PP4 activity, with broad cellular effects, highlighting FBXO42 as a novel regulatory node in ubiquitin-mediated signalling for future therapeutic exploitation.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月3日

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  • Hongbin Yang,
  • Paul Smith,
  • Yingying Ma,
  • Emily Southworth,
  • Varun Gopala Krishna,
  • Beatrice Salerno,
  • Joseph Rowland,
  • Alexander E P Loftus,
  • Domenico Grieco,
  • Iolanda Vendrell,
  • Roman Fischer,
  • Benedikt M Kessler,
  • Vincenzo D’Angiolella

摘要

F-box proteins are the substrate recognition modules of the SCF (SKP1–Cullin–F-box) E3 ubiquitin ligase complex. FBXO42, an understudied member of this family, has recently emerged as a modulator of key cellular processes, including cell cycle progression, the DNA damage response, and glioma stem cell survival. In this study, we define the function of FBXO42 as a major regulator of the protein phosphatase PP4. Phosphoprotein phosphatases (PPPs) have a broad array of substrates, hence necessitating tight regulation. We observe that FBXO42 ubiquitinates the PP4 complex to govern the assembly of regulatory and catalytic subunits, with the net effect of restraining the latter’s phosphatase activity. FBXO42 depletion unleashes PP4 activity, with broad cellular effects, highlighting FBXO42 as a novel regulatory node in ubiquitin-mediated signalling for future therapeutic exploitation.