Tuning of the RBR1-E2F/DP transcriptional module by the F-box protein FBL17
F-box proteins of SCF E3 ligases have been documented to control the abundance of numerous critical regulatory proteins. In <i>Arabidopsis</i>, 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. <i>FBL17</i> 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 <i>E2Fa</i> or <i>E2Fb</i> do not alleviate the severe <i>fbl17</i> phenotype but worsen it. By contrast, it is the accumulation of the transcriptional repressor E2Fc that causes <i>fbl17</i> 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.
Authors
- Naomie Gentric (ORCID: https://orcid.org/0000-0003-0624-1887)
- Cécile Raynaud (ORCID: https://orcid.org/0000-0002-5231-8120)
- Johana Chicher (ORCID: https://orcid.org/0000-0002-4403-7484)
- David Latrasse (ORCID: https://orcid.org/0000-0003-2149-0128)
- Thomas Potuschak (ORCID: https://orcid.org/0000-0002-2632-4981)
- Crisanto Gutiérrez (ORCID: https://orcid.org/0000-0001-8905-8222)
- Sandra Noir (ORCID: https://orcid.org/0000-0002-5666-2885)
- Ting Pan (ORCID: https://orcid.org/0000-0003-0146-6278)
- Shunping Yan
- Bénédicte Desvoyes
- Zoltán Magyar
- Philippe Hammann
- Xiaoning He
- Juliette Espanet
- Aladár Pettkó-Szandtner
- Rim Brik
- Moussa Benhamed
Institutions
- Centre National de la Recherche Scientifique (FR)
- Huazhong Agricultural University (CN)
- Université Paris-Saclay (FR)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut des Sciences des Plantes de Paris Saclay (FR)
- Institute of Biochemistry (HU)
- Institut de Biologie Moléculaire des Plantes (FR)
- Institute of Plant Biology (HU)
- Centro de Biología Molecular Severo Ochoa (ES)
- Universidad Autónoma de Madrid (ES)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2026-02-18
- DOI
- https://doi.org/10.1126/sciadv.adz2439
- Primary Topic
- Cancer-related Molecular Pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.00