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Tpx1 (UniProt O74887) is the single typical 2-Cys peroxiredoxin (thioredoxin peroxidase,
EC 1.11.1.24) of S. pombe, reducing hydrogen peroxide and organic peroxides via a
peroxidatic Cys48 and resolving Cys169, recycled by the thioredoxin system.
"Tpx1 functions as a **thioredoxin-dependent peroxidase** that detoxifies **hydrogen peroxide** and can also reduce **organic peroxides**, consistent with its classification as a typical 2‑Cys peroxiredoxin. Experimentally, *tpx1* deletion causes extreme peroxide sensitivity and increased oxidative damage markers (e.g., protein carbonylation), supporting a central peroxide-detoxifying role in vivo."
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Tpx1 is recycled primarily by the cytosolic thioredoxin system, with Trx1 the main
electron donor (Trx3 partially compensatory) and Trr1/NADPH maintaining the reduced
thioredoxin pool.
"Trx1 is described as the main electron donor for Tpx1, with **Trx3** reported as partially compensatory when Trx1 is absent; thioredoxin reductase (**Trr1**) maintains the thioredoxin pool using NADPH."
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Beyond detoxification, Tpx1 is a central H2O2 sensor/redox relay that routes peroxide
information to two major stress branches: the Pap1 (AP-1-like) transcription factor and
the Sty1/Atf1 stress-activated MAPK pathway.
"A defining feature of *S. pombe* Tpx1 is that it is not only an antioxidant enzyme but also a **central peroxide sensor/transducer** that routes H2O2 information to at least two major oxidative stress response branches: **Pap1** (AP‑1-like) and the **Sty1/Atf1** stress-activated MAPK pathway."
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Under mild H2O2 (~0.2 mM), Tpx1 is required for Pap1 oxidation/activation, nuclear
accumulation and downstream antioxidant gene induction, acting as the primary peroxide
sensor/transducer for the Pap1 pathway.
"Tpx1 is reported to be required for **Pap1 oxidation/activation** under mild peroxide stress, acting as the primary peroxide sensor/transducer for this pathway; Pap1 nuclear accumulation and downstream gene induction depend on Tpx1-mediated redox control."
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The Tpx1 signaling (Sty1) role can be genetically uncoupled from its peroxidase activity
using separation-of-function alleles such as tpx1C169S, which disrupts thioredoxin
peroxidase activity while leaving Sty1 regulation intact.
"role in Sty1 pathway signaling can be genetically separated from its thioredoxin peroxidase activity using alleles such as **tpx1C169S**, described as disrupting thioredoxin peroxidase activity while leaving Sty1 regulation intact."
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At high peroxide flux Tpx1 is hyperoxidized to a sulfinic acid, which inactivates its
thioredoxin-dependent peroxidase activity; sulfiredoxin (Srx1) repairs the hyperoxidized
form in an ATP-dependent reaction, gating signaling over time.
"which **inactivates thioredoxin-dependent peroxidase activity** because thioredoxin cannot directly reduce the sulfinic form. Hyperoxidized typical 2‑Cys Prxs can be repaired by **sulfiredoxin (Srx)** via an **ATP-dependent** reaction, restoring catalytic competence and changing signaling capacity over time."
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Tpx1 directly relays peroxide signals to regulatory proteins, forming protein-protein
disulfide complexes with partners such as Pka1 and Csn5 in response to 0.2 mM H2O2.
"Pka1 and Csn5 form **protein–protein disulfide complexes with Tpx1** in response to **0.2 mM H2O2**, consistent with Tpx1 functioning as a redox relay to regulatory proteins."
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Tpx1 is predominantly cytosolic before and after H2O2 exposure, with a minor
mitochondrial intermembrane-space (IMS) pool detected under oxidative conditions.
"Tpx1 is primarily described as **cytosolic** before and after H2O2 exposure, consistent with its roles in controlling cytosolic thioredoxins and transcription factor signaling."