Plant employs NLR receptors to recognize isolate-specific effectors and induce massive transcriptional reprogramming for effective defense responses.Some plant NLRs function inside nucleus to trigger immune responses by interacting with transcription factors(TFs)acting as transcription repressor or activator.Barley Mla locus encodes allelic MLA NLR receptors each recognizing specific powdery mildew fungal isolate and triggering disease resistance against powdery mildew fungus through the nucleus.However,how MLAs engage with the transcription machinery and initiate defense gene transcriptions is not fully understood.Here,we show that activated MLA1 associates with the base subcomplex of 19S regulatory particle(19S RP)that is located at the ends of the 20S core particle of 26S proteasome.MLA activation lead to the recruitment of a CREB-Binding Protein(CBP)acetyltransferase to target a WRKY2 transcription repressor for acetylation and proteasomal degradation,which is required for the full induction of defense gene expressions and MLA-mediated disease resistance.Our data reveal a novel mechanism of plant NLR-mediated immunity whereby activated NLRs rely on 19S RP to recruit a acetyltransferase to target and remove a transcriptional repressor by acetylation coupled ubiquitination and degradation.