title: The Proteasome Stress Regulon Is Controlled by a Pair of NAC Transcription Factors in Arabidopsis.
abstract: Proteotoxic stress, which is generated by the accumulation of unfolded or aberrant proteins due to environmental or cellular perturbations, can be mitigated by several mechanisms, including activation of the unfolded protein response and coordinated increases in protein chaperones and activities that direct proteolysis, such as the 26S proteasome. Using RNA-seq analyses combined with 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 This network includes 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 transcriptional 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/CUC2 78 (NAC78) 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 heterodimerize, 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.
authors.affiliation: Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Gladman
authors.affiliation: Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706 Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Marshall
authors.affiliation: Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706 Department of Biology, Washington University in St. Louis, St. Louis, Missouri 63130 rdvierstra@wustl.edu.
authors.forename: Richard D
authors.identifier: 0000-0003-0210-3516
authors.initials: RD
authors.lastname: Vierstra
mesh_terms: D017360:Arabidopsis / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D000069286:Bortezomib / Q000494:pharmacology; D018506:Gene Expression Regulation, Plant / Q000187:drug effects / Q000235:genetics; D007976:Leupeptins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D018085:Regulon / Q000187:drug effects / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D007976:Leupeptins; D014157:Transcription Factors; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde