XCP1 is a caspase that proteolyzes Pathogenesis-related protein 1 to produce the cytokine CAPE9 for systemic immunity in Arabidopsis

Abstract Proteolytic activation of cytokines regulates immunity in diverse organisms. In animals, cysteine-dependent aspartate-specific proteases (caspases) play central roles in cytokine maturation. Although the proteolytic production of peptide cytokines is also essential for plant immunity, evidence for a plant caspase is still lacking. In this study, we discovered that proteolysis of a caspase-like substrate motif “CNYD” within Pathogenesis-related protein 1 (AtPR1) in Arabidopsis generates an immunomodulatory cytokine (AtCAPE9). Salicylic acid enhances CNYD-targeted protease activity and the proteolytic release of AtCAPE9 from AtPR1 in Arabidopsis. We show that this process involves a caspase, identified as Xylem cysteine peptidase 1 (XCP1). XCP1 exhibits a calcium-modulated pH-activity profile and a comparable activity to human caspases. XCP1 is required to induce systemic immunity triggered by pathogen-associated molecular patterns. This work reveals XCP1 as the first known plant caspase, which produces the cytokine AtCAPE9 from the canonical salicylic acid signaling marker PR1 to activate systemic immunity.