Prdx1 Interacts with ASK1 upon Exposure to H₂O₂ and Independently of a Scaffolding Protein

• Main Authors: Trung Nghia Vo, Julia Malo Pueyo, Khadija Wahni, Daria Ezeriņa, Jesalyn Bolduc, Joris Messens
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: Antioxidants
• Subjects: peroxiredoxin; redox communication; hydrogen peroxide; Prx1; Prdx1; Prdx2
• Online Access: https://www.mdpi.com/2076-3921/10/7/1060

Hydrogen peroxide (H₂O₂) is a key redox signaling molecule that selectively oxidizes cysteines on proteins. It can accomplish this even in the presence of highly efficient and abundant H₂O₂ scavengers, peroxiredoxins (Prdxs), as it is the Prdxs themselves that transfer oxidative equivalents to specific protein thiols on target proteins via their redox-relay functionality. The first evidence of a mammalian cytosolic Prdx-mediated redox-relay—Prdx1 with the kinase ASK1—was presented a decade ago based on the outcome of a co-immunoprecipitation experiment. A second such redox-relay—Prdx2:STAT3—soon followed, for which further studies provided insights into its specificity, organization, and mechanism. The Prdx1:ASK1 redox-relay, however, has never undergone such a characterization. Here, we combine cellular and in vitro protein–protein interaction methods to investigate the Prdx1:ASK1 interaction more thoroughly. We show that, contrary to the Prdx2:STAT3 redox-relay, Prdx1 interacts with ASK1 at elevated H₂O₂ concentrations, and that this interaction can happen independently of a scaffolding protein. We also provide evidence of a Prdx2:ASK1 interaction, and demonstrate that it requires a facilitator that, however, is not annexin A2. Our results reveal that cytosolic Prdx redox-relays can be organized in different ways and yet again highlight the differentiated roles of Prdx1 and Prdx2.