**Abstract**

Any condition that disrupts the ER homeostasis activates a cytoprotective signaling cascade, designated as the unfolded protein response (UPR), which is transduced in plant cells by a bipartite signaling module. Activation of IRE1/ bZIP60 and bZIP28/bZIP17, which represent the bipartite signaling arms and serve as ER stress sensors and transducers, results in the upregulation of ER protein processing machinery-related genes to recover from stress. However, if the ER stress persists and the cell is unable to restore ER homeostasis, programmed cell death signaling pathways are activated for survival. Here, we describe an ER stress-induced plant-specific cell death program, which is a shared response to multiple stress signals. This signaling pathway was first identified through genome-wide expression profile of differentially expressed genes in response to combined ER stress and osmotic stress. Among them, the development and cell death domain-containing N-rich proteins (DCD/NRPs), *NRP-A* and *NRP-B*, and the transcriptional factor *GmNAC81* were selected as mediators of cell death in plants. These genes were used as targets to identify additional components of the cell death pathway, which is described here as a regulatory circuit that integrates a stress-induced cell death program with leaf senescence via the NRP-A/NRP-B/GmNAC81:GmNAC30/VPE signaling module.

**Keywords:** senescence, stress, NRP, DCD, BiP, NAC, VPE, ER, osmotic stress, drought

## **1. Introduction**

The onset of leaf senescence is a highly regulated developmental program that is controlled by both genetics and the environment. Multiple stresses in plants induce programmed cell death, and the underlying regulatory mechanisms are often associated with molecular links of developmentally programmed senescence. The transcriptome changes induced by different environmental stressors are not

entirely overlapping, but functional analysis of genes commonly induced as shared responses can give clues on signaling integration. This approach has been used to select for overlapping genes as candidate regulatory components that integrate the ER stress and osmotic stress responses, which were shown later to participate also in natural leaf senescence. Among genes identified as components of the ER and osmotic stress shared response, the developmental and cell death (DCD) domaincontaining asparagine-rich proteins (NRP-A and NRP-B) were the first ones to be characterized as cell death-promoting proteins, and hence this multiple stressintegrating signaling was designated as stress-induced DCD/NRP-mediated cell death response. Further characterization of the cell death pathway implicated in the discovery of the signaling module ERD15/NRPs/GmNAC81:GmNAC30/VPE that also has been shown to operate in developmentally programmed leaf senescence. This plant-specific cell death signaling module, which operates in both stressinduced and natural leaf senescence, constitutes the primary focus of this chapter.
