biostudies-literatureSato YMEXT | JST | Fusion Oriented REsearch for disruptive Science and TechnologyJapan Society for the Promotion of Science LondonCanon Medical Systems Corporation (Canon Medical)Canon Medical Systems CorporationJapan Society for the Promotion of Science London (JSPS)MEXT | JST | Fusion Oriented REsearch for disruptive Science and Technology (FOREST)e2414618121https://www.ebi.ac.uk/biostudies/studies/S-EPMC11474076biostudies-literatureUnknown121(41)The transcription factor E2F1 serves as a regulator of the cell cycle and promotes cell proliferation. It is highly expressed in cancer tissues and contributes to their malignant transformation. Degradation by the ubiquitin-proteasome system may help to prevent such overexpression of E2F1 and thereby to suppress carcinogenesis. A detailed understanding of the mechanisms underlying E2F1 degradation may therefore inform the development of new cancer treatments. We here identified SCF^FBXW7 as a ubiquitin ligase for E2F1 by comprehensive analysis. We found that phosphorylation of E2F1 at serine-403 promotes its binding to FBXW7 (F-box/WD repeat-containing protein 7) followed by its ubiquitination and degradation. Furthermore, calcineurin, a Ca²⁺/calmodulin-dependent serinProceedings of the National Academy of Sciences of the United States of AmericaCalcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit.PMC11474076S22-004721H0240324K02227JPMJFR2065Hanaki STomiyasu HMiyamoto TKobayashi DSakurai MMasaki TMorimoto MHabara MShimada MSato YMiki YfalseCalcineurin-mediated dephosphorylation stabilizes E2F1 protein by suppressing binding of the FBXW7 ubiquitin ligase subunit.The transcription factor E2F1 serves as a regulator of the cell cycle and promotes cell proliferation. It is highly expressed in cancer tissues and contributes to their malignant transformation. Degradation by the ubiquitin-proteasome system may help to prevent such overexpression of E2F1 and thereby to suppress carcinogenesis. A detailed understanding of the mechanisms underlying E2F1 degradation may therefore inform the development of new cancer treatments. We here identified SCF^FBXW7 as a ubiquitin ligase for E2F1 by comprehensive analysis. We found that phosphorylation of E2F1 at serine-403 promotes its binding to FBXW7 (F-box/WD repeat-containing protein 7) followed by its ubiquitination and degradation. Furthermore, calcineurin, a Ca²⁺/calmodulin-dependent serin2024-01-01T00:00:00Z2024 Oct2025-06-28T03:05:19.341Z2025-06-28T03:05:19.341ZS-EPMC114740763936164110.1073/pnas.2414618121