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 speci

8月7日から9日まで開催されていた香港オーディオショウにて、イヤホン関連にもいくつか興味深いトピックが発表された。Unique Melodyからは、イヤホン＋専用アンプの「PP6 Pro＆UM Raptor」が登場したほか、DITA、Forte Earsもプロトタイプ製品を展示し話題を集めていた。

Functional genome-wide knockout and focused base editing screens uncover CYB5R4 as an evolutionarily conserved reductase for the active site metal ions of the PP4 and PP6 phosphoprotein phosphatases.