| dc.description.abstract |
The diversity and complexity of living organisms are driven by the specificity of their proteome, which is tightly regulated through controlled protein production, utilization, and degradation. To mediate this regulation, conserved and sophisticated mechanisms have evolved to form a molecular network that maintains cellular protein homeostasis, known as proteostasis. Among
these mechanisms, proteolytic pathways are key determinants in proteome regulation, with proteolysis being essential for clearing unwanted proteins, especially under environmental stress. In eukaryotes, the primary proteolytic pathway is the ubiquitin-proteasome system (UPS). This system relies on the post-translational modification of target proteins with ubiquitin peptides, which marks them for recognition and specific degradation by the 26S proteasome
holoenzyme. The latter identifies ubiquitinated substrates, unfolds them, and degrades them via a proteolytic core. Proteasomal degradation is responsible for the majority of protein turnover in cells and is crucial for maintaining cellular proteome balance. Under stress, however, the accumulation of proteasome substrates can exceed proteasomal capacity, resulting in proteotoxic stress. Defects in proteasomal turnover are associated with numerous medical and agricultural challenges. To counteract such stress, eukaryotes have evolved a feedback mechanism that ensures adequate proteasomal capacity. This mechanism involves a negative feedback loop in which transcriptional activators of proteasome genes are
themselves substrates for proteasomal degradation, enabling constant monitoring of proteasome capacity and a rapid response under stress conditions. While this mechanism has been characterized in yeast and mammals, it remains poorly understood in plants. In this study, we investigated the role of proteolytic pathways in plant-pathogen interactions, with a focus on the importance of the ubiquitin-proteasome system in this context. We developed a pipeline to assess proteasome status under stress conditions and characterized the proteasome feedback loop in plants. We found that a sorting mechanism at the endoplasmic reticulum mediates both the degradation and nuclear translocation of the proteasome
transcriptional activators NAC53 and NAC78 when proteasomal capacity is exceeded. Once in the nucleus, NAC53 and NAC78 activate proteasome gene expression and simultaneously repress photosynthesis-associated nuclear genes. This cross-talk enables an increase in proteasome capacity while reducing the accumulation of proteasome substrates. We identified
this cross-talk as a core response to stress in plants. This work reveals an intricate regulatory network linking protein production, degradation, and energy metabolism, providing a conceptual framework for further exploration of proteostasis maintenance in eukaryotes. |
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