ArticleNature communications2026
A functional map of phosphoprotein phosphatase regulation identifies an evolutionarily conserved reductase for the catalytic metal ions.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Shifting paradigms: phosphatases from basic biology to druggable targets.Biology open · 2026Article
- The nitrogen starvation-induced inhibitor Rts3 restrains Sit4/PP6 to gate quiescence downstream of TORC1.Nature communications · 2026Article
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18 authors.
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Abstract
Serine/threonine phosphoprotein phosphatases (PPPs) are conserved metalloenzymes and key regulators of intracellular signaling. Here, we systematically map the components and residues required for PP2A-like phosphatase (PP2A/PP4/PP6) function using genome-wide CRISPR knockout and focused base editing screens and provide this as a comprehensive resource. We uncover the reductase CYB5R4 as an evolutionarily conserved activator of PP4 and PP6, but not PP2A. We demonstrate that PP4 and PP6 are redox sensitive and require CYB5R4 to reduce the active site metal ions for activation. Mechanistically, this involves the selective binding of PP4 and PP6 through binding elements in the N-terminal tail of CYB5R4 and CYB5R4-bound heme serving as an electron donor for the active site. We further show that this activation is critical for regulating the response to DNA damage. Our work hints that active site metal ion redox regulation mediates crosstalk between the oxidative state of the cell and specific phosphatase activities.
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