|LEE, KWANG-HEE - University Of Wisconsin|
|VIERSTRA, RICHARD - University Of Wisconsin|
Submitted to: The Plant Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/11/2016
Publication Date: 7/1/2016
Citation: Gladman, N., Lee, K., Vierstra, R. 2016. The proteasome stress regulon is controlled by a pair of NAC transcription factors in arabidopsis. The Plant Cell. 28:1279-1296.
Interpretive Summary: We characterized a set of genes that are transcriptionally upregulated while specifically inhibiting 26S proteasome function in Arabidopsis, and showed the relationship between this set of genes and other conserved stress-responsive pathways (e.g. heat shock and oxidative stress). Additionally, we identified two plant-specific transcription factors, NAC53 and NAC78, that redundantly control the expression of this gene suite during proteasome-specific stress, and that plants lacking both of these transcription factors are unable to survive proteasome inhibition. We conclude that these transcription factors are major regulators of the proteasome stress response in Arabidopsis and likely have similar roles in other land plants.
Technical Abstract: Proteotoxic stress is mitigated by a variety of mechanisms, including activation of the unfolded protein response and co-ordinated increases in protein chaperones and activities that direct proteolysis such as the 26S proteasome. Using RNA-seq analyses combined with either chemical inhibitors or mutants that induce proteotoxic stress by impairing 26S proteasome capacity, we defined the transcriptional network that responds to this stress in Arabidopsis thaliana. Included are genes encoding core and assembly factors needed to build the complete 26S particle, alternative proteasome capping factors, enzymes involved in protein ubiquitylation/deubiquitylation and cellular detoxification, protein chaperones, autophagy components, and various transcription regulators. Many loci in this proteasome-stress regulon contain a consensus cis element upstream of the transcription start site, which was previously identified as a binding site for the NAM/ATAF1,2/CUC2 (NAC)-78 transcription factor. Double mutants disrupting NAC78 and its closest relative NAC53 are compromised in the activation of this regulon, and notably are strongly hypersensitive to the proteasome inhibitors MG132 and bortezomib. Given that NAC53 and NAC78 homo- and hetero-dimerize, we propose that they work as a pair in activating the expression of numerous factors that help plants survive proteotoxic stress, and thus play a central regulatory role in maintaining protein homeostasis.