FBXL2 is a ubiquitin E3 ligase subunit that triggers mitotic arrest.
Mitotic progression is regulated by ubiquitin E3 ligase complexes to carefully orchestrate eukaryotic cell division. Here, we show that a relatively new E3 ligase component belonging to the SCF (Skip-Cullin1-F-box protein) E3 ligase family, SCF (FBXL2) , impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation. Both cyclin D3 and FBXL2 colocalize within the centrosome. FBXL2 overexpression led to G 2/M-phase arrest in transformed epithelia, resulting in the appearance of supernumerary centrosomes, tetraploidy and nuclei where condensed chromosomes are arranged on circular monopolar spindles typical of mitotic arrest. RNAi-mediated knockdown of cyclin D3 recapitulated effects of SCF (FBXL2)  expression. SCF (FBXL2)  impaired the ability of cyclin D3 to associate with centrosomal assembly proteins [Aurora A, polo-like kinase 4 (Plk4), CDK11]. Thus, these results suggest a role for SCF (FBXL2)  in regulating the fidelity of cellular division.
Department of Medicine, Acute Lung Injury Center of Excellence, The University of Pittsburgh, Pittsburgh, PA, USA. chenb@upmc.edu
Bill B
BB
Chen
Jennifer R
JR
Glasser
Tiffany A
TA
Coon
Rama K
RK
Mallampalli
D000704:Analysis of Variance; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000502:physiology*; D002460:Cell Line; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000378:metabolism*; D005453:Fluorescence; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D034622:RNA Interference; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D056743:Cyclin D3; D044783:F-Box Proteins; C558726:FBXL2 protein, mouse; D044767:Ubiquitin-Protein Ligases