Division of Redox Regulation, DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, 69120, Heidelberg, Germany.
Nat Commun. 2020 Sep 9;11(1):4512. doi: 10.1038/s41467-020-18324-9.
Hydrogen peroxide (HO) is recognized to act as a signaling molecule. Peroxiredoxins (Prxs) have the ability to transfer HO-derived oxidizing equivalents to redox-regulated target proteins, thus facilitating the transmission of HO signals. It has remained unclear how Prxs and their target proteins are brought together to allow for target-specific protein thiol oxidation. Addressing the specific case of Prx2-dependent STAT3 oxidation, we here show that the association of the two proteins occurs prior to Prx oxidation and depends on a scaffolding protein, the membrane chaperone annexin A2. Deletion or depletion of annexin A2 interrupts the transfer of oxidizing equivalents from Prx2 to STAT3, which is observed to take place on membranes. These findings support the notion that the Prx2-STAT3 redox relay is part of a highly organized membrane signaling domain.
过氧化氢（HO）被认为是一种信号分子。过氧化物酶（Prxs）能够将 HO 衍生的氧化当量转移到氧化还原调节的靶蛋白上，从而促进 HO 信号的传递。然而，Prxs 及其靶蛋白如何聚集在一起以允许针对特定蛋白的巯基氧化仍然不清楚。针对 Prx2 依赖性 STAT3 氧化的具体情况，我们在此表明，两种蛋白的关联发生在 Prx 氧化之前，并且依赖于一种支架蛋白，即膜伴侣蛋白 annexin A2。annexin A2 的缺失或耗竭会中断从 Prx2 到 STAT3 的氧化当量转移，而这种转移发生在膜上。这些发现支持了这样一种观点，即 Prx2-STAT3 氧化还原接力是高度组织化的膜信号域的一部分。
