Tuning of the RBR1-E2F/DP transcriptional module by the F-box protein FBL17

Espanet, Juliette and He, Xiaoning and Pan, Ting and Gentric, Naomie and Potuschak, Thomas and Desvoyes, Bénédicte and Hammann, Philippe and Chicher, Johana and Brik, Rim and Lechner, Esther and Latrasse, David and Pettkó-Szandtner, Aladár and Gutierrez, Crisanto and Raynaud, Cécile and Magyar, Zoltán and Benhamed, Moussa and Yan, Shunping and Noir, Sandra and Genschik, Pascal (2026) Tuning of the RBR1-E2F/DP transcriptional module by the F-box protein FBL17. SCIENCE ADVANCES, 12 (8). No. eadz2439. ISSN 2375-2548

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Abstract

F-box proteins of SCF E3 ligases have been documented to control the abundance of numerous critical regulatory proteins. In Arabidopsis , one of them, F-BOX-LIKE17 (FBL17), stands out for playing a key role in DNA replication, DNA damage, and, more recently, for the control of cell size. FBL17 null mutants exhibit severe cellular defects leading to lethality. However, the molecular mechanisms by which FBL17 operate remain poorly understood. Here, we show that FBL17 interacts with different components of the RETINOBLASTOMA-RELATED1/E2F module and is involved in the protein turnover of E2Fa and E2Fb. However, mutations in E2Fa or E2Fb do not alleviate the severe fbl17 phenotype but worsen it. By contrast, it is the accumulation of the transcriptional repressor E2Fc that causes fbl17 mutant lethality. Our results highlight a key role for FBL17 in modulating the transcriptional control of E2F target genes ensuring precise control of cell cycle progression and avoiding uncontrolled DNA damage response.

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