A New Twist on Systemic Acquired Resistance: Redox Control of the NPR1–TGA1 Interaction by Salicylic Acid

Systemic acquired resistance (SAR) is a form of broad-range disease resistance in plants that develops after exposure to certain avirulent necrotizing pathogens. Induction of SAR is dependent on the accumulation of the endogenous signaling molecule salicylic acid (SA) and the transmission of the SA signal via the activity of the key regulatory protein NONEXPRESSOR OF PATHOGENESIS-RELATED PROTEINS1 (NPR1). Resistance is conferred in large part by the SAand NPR1-dependent activation of PR genes and the accumulation of PR proteins, some of which have antimicrobial activity. Although a number of key players in the development of SAR have been identified, the fundamental mechanism(s) of SA signal transduction remains unknown. The basic model of SA action in SAR states that SA accumulation causes the translocation of NPR1 into the nucleus, where it interacts with members of the TGA family of transcription factors and enhances the binding of these factors to SA response elements in the promoters of PR genes, thus ultimately affecting the transcription of numerous genes in the SAR pathway (Després et al., 2000; Kinkema et al., 2000; Zhou et al., 2000; Subramaniam et al., 2001; Fan and Dong, 2002). The mechanism by which the nuclear translocation of NPR1 is effected is unclear. Furthermore, the in vivo interaction of NPR1 with TGA proteins is dependent on induction by SA, even though TGA proteins are expressed constitutively in the nucleus and some NPR1 protein is localized to the nucleus as well as the cytoplasm of unstimulated tissue. In other words, SA is thought to stimulate the enhanced nuclear translocation of NPR1 and to activate the protein (or its interacting TGA partner) to stimulate the interaction with TGA factors. In this issue of The Plant Cell , Després et al. (pages 2181–2191) show that redox changes influenced by SA control the interaction of NPR1 and TGA1, thus enhancing the DNA binding activity of TGA1. The authors show that SA modulates the redox state of TGA1 in vivo, via the reduction of two Cys residues that form a disulfide bridge in the absence of SA, and that NPR1 interacts specifically with the reduced form of TGA1 (Figure 1). They further show that DNA binding activity per se of TGA1 is not affected by the redox status; rather, the redox-regulated interaction with NPR1 enhances the DNA binding of TGA1. These results demonstrate that TGA1 and TGA4 are likely to be functional interacting partners of NPR1 in the development of SAR and that the redox regulation of these factors confers an additional level of control over their interaction. NPR1 was identified previously as a key factor in SA-regulated PR gene expression and the development of SAR because disease resistance and the SA-induced expression of PR genes are compromised severely in npr1 mutant plants (Cao et al., 1994; Delaney et al., 1995; Glazebrook et al., 1996; Shah et al., 1997). NPR1 contains a nuclear localization domain at the C terminus and two known protein–protein interaction domains: a BTB/POZ domain at the N terminus and an ankyrin repeat domain near the center of the protein sequence (Cao et al., 1997; Ryals et al., 1997). The presence of protein–protein interaction domains and the absence of a DNA binding domain, together with the mutant phenotype, suggest that NPR1 Figure 1. SA-Mediated Redox Control of TGA1.