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Although the function of ubiquitin\u2010protein ligases (E3s) in plants response to diverse abiotic stress by targeting specific substrates has been well studied, the involvement of E2s in environmental responses and their downstream targets are not well understood. In this study, we demonstrated that the E2 ubiquitin\u2010conjugating enzyme 18 (UBC18) influences the stability of FREE1 to modulate iron deficiency stress. UBC18 affects the ubiquitination of FREE1 and promotes its degradation, and overexpression of <jats:italic>UBC18<\/jats:italic> decreases plants\u2019 sensitivity to iron deficiency by reducing FREE1 level, whereas the <jats:italic>ubc18<\/jats:italic> mutant exhibits sensitivity due to elevated FREE1 accumulation. This study also identified that lysine residues K227, K295, K315, and K540 are required for FREE1 ubiquitination and stability regulation. Mutating these lysine residues in FREE1 resulted in plants\u2019 sensitivity to iron starvation. Taken together, our findings shed light on the mechanism of UBC18 in responding to iron deficiency stress by modulating the abundance of FREE1, and further elucidate the role of ubiquitination sites in FREE1 stability regulation and the plant iron deficiency response.<\/jats:p>","DOI":"10.1111\/tpj.17077","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T18:14:59Z","timestamp":1729102499000},"page":"1751-1763","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>UBC18 E2<\/scp> conjugating enzyme depends on <scp>SINAT1 E3<\/scp> ligase to destabilize the <scp>ESCRT<\/scp> component <scp>FREE1<\/scp> in plant iron deficiency responses"],"prefix":"10.1111","volume":"120","author":[{"given":"Chuanliang","family":"Liu","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences South China Normal 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