title: FBXO31 protects against genomic instability by capping FOXM1 levels at the G2/M transition.
abstract: F-box proteins in conjunction with Skp1, Cul1 and Rbx1 generate SCF complexes that are responsible for the ubiquitination of proteins, leading to their activation or degradation. Here we show that the F-box protein FBXO31 is required for normal mitotic progression and genome stability due to its role in regulating FOXM1 levels during the G2/M transition. FBXO31-depleted cells undergo a transient delay in mitosis due to an activated spindle checkpoint concomitant with an increase in lagging chromosomes and anaphase bridges. FBXO31 regulates mitosis in part by controlling the levels of FOXM1, a transcription factor and master regulator of mitosis. FBXO31 specifically interacts with FOXM1 during the G2/M transition, resulting in FOXM1 ubiquitination and degradation. FBXO31 depletion results in increased expression of FOXM1 transcriptional targets and mimics the FOXM1 overexpression. In contrast, co-depletion of FBXO31 and FOXM1 restores the genomic instability phenotype but not the delay in mitosis, indicating that FBXO31 probably has additional mitotic substrates. Thus, FBXO31 is the first described negative regulator of FOXM1 during the G2/M transition.
authors: Signal Transduction Laboratory, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: J M
authors: JM
authors: Jeffery
authors: Signal Transduction Laboratory, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: M
authors: M
authors: Kalimutho
authors: Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: P
authors: P
authors: Johansson
authors: Signal Transduction Laboratory, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: D G
authors: DG
authors: Cardenas
authors: Department of Paediatrics, School of Medicine and the Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia.
authors: R
authors: R
authors: Kumar
authors: Signal Transduction Laboratory, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: K K
authors: KK
authors: Khanna
mesh_terms: D002455:Cell Division / Q000235:genetics*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D016195:G2 Phase / Q000235:genetics*; D042822:Genomic Instability; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D044783:F-Box Proteins; C507917:FBXO31 protein, human; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D025521:Tumor Suppressor Proteins