{"doi":"10.1111/tpj.70478","title":"Bimodal retrograde signaling disrupts a suppressor network and activates a key transcriptional activator to direct stress responses","abstract":"SUMMARY Plastid‐to‐nucleus communication, crucial for regulating stress‐responsive gene expression, has long intrigued researchers. This study reveals how the plastidial metabolite 2‐C‐methyl‐D‐erythritol‐2,4‐cyclopyrophosphate (MEcPP) orchestrates transcriptional reprogramming by modulating the rapid stress response element (RSRE), a conserved regulatory hub in the plant general stress response network. Yeast one‐hybrid assays identified HAT1, a class II HD‐Zip protein, as a negative regulator of RSRE. Genetic analyses, including HAT1 overexpression and knockdowns, confirmed its role in suppressing RSRE activity. Interaction assays uncovered a suppression network involving HAT1, the co‐repressor TOPLESS (TPL), and the nuclear importin IMPα‐9. Furthermore, HAT1 interacts with calmodulin‐binding transcription activator 3 (CAMTA3), a calcium/calmodulin‐binding transcription factor known to activate RSRE. AlphaFold modeling provided insights into the architecture of the HAT1‐RSRE complex and HAT‐CAMTA3 interaction, supported by conserved domains across plant species. Under stress condition, MEcPP accumulation promotes the 26S proteasomal degradation of TPL and IMPα‐9 while reduces auxin‐dependent HAT1 expression. Additionally, MEcPP enhances Ca 2+ influx, activating CAMTA3 and enabling it to bind RSRE, thereby initiating the transcription of stress response genes. This dual mechanism—dismantling suppressors (HAT1, TPL, and IMPα‐9) and activating CAMTA3—underscores MEcPP's central role in plastid‐to‐nucleus signaling. These findings emphasize MEcPP's pivotal function in dynamically regulating gene expression to maintain cellular homeostasis under environmental stress.","journal":"The Plant Journal","year":2025,"id":542347,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1235853,"name":"Jingzhe Guo","orcid":"0000-0003-0858-527X","position":1,"is_corresponding":false},{"id":1393591,"name":"Carlos Rodríguez","orcid":"0000-0002-7438-8963","position":2,"is_corresponding":false},{"id":1235852,"name":"María Fernanda Gómez-Méndez","orcid":"0000-0002-2107-5875","position":3,"is_corresponding":false},{"id":912441,"name":"Yaqi Wang","orcid":"0000-0003-0001-9687","position":4,"is_corresponding":false},{"id":1431426,"name":"Wilhelmina van de Ven","orcid":"0000-0001-8709-7412","position":5,"is_corresponding":false},{"id":771658,"name":"Malathy Palayam","orcid":"0000-0001-7031-947X","position":6,"is_corresponding":false},{"id":583671,"name":"José L. Pruneda-Paz","orcid":"0000-0002-0054-0918","position":7,"is_corresponding":false},{"id":853229,"name":"Nitzan Shabek","orcid":"0000-0002-2190-5955","position":8,"is_corresponding":false},{"id":483225,"name":"Katayoon Dehesh","orcid":"0000-0002-9312-8032","position":9,"is_corresponding":false},{"id":483219,"name":"Liping Zeng","orcid":"0000-0002-3579-9145","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-19T02:52:55.809501Z","pmid":"40977442","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}