FBXL2 is a ubiquitin E3 ligase subunit that triggers mitotic arrest |
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| Authors: | Bill B Chen Jennifer R Glasser Tiffany A Coon Rama K Mallampalli |
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| Institution: | 1.Department of Medicine; The University of Pittsburgh; Pittsburgh, PA USA;2.Acute Lung Injury Center of Excellence; The University of Pittsburgh; Pittsburgh, PA USA;3.Department of Cell Biology and Physiology; The University of Pittsburgh; Pittsburgh, PA USA;4.Medical Specialty Service Line; Veterans Affairs Pittsburgh Healthcare System; Pittsburgh, PA USA |
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| Abstract: | 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, SCFFBXL2, impairs cell proliferation by mediating cyclin D3 polyubiquitination and degradation. Both cyclin D3 and FBXL2 colocalize within the centrosome. FBXL2 overexpression led to G2/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 SCFFBXL2 expression. SCFFBXL2 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 SCFFBXL2 in regulating the fidelity of cellular division.Key words: F-box protein, centrosome, mitosis, cyclin D3, Aurora A |
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