期刊
CELL CYCLE
卷 10, 期 20, 页码 3487-3494出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.10.20.17742
关键词
F-box protein; centrosome; mitosis; cyclin D3; Aurora A
类别
资金
- US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development
- US Department of Veterans Affairs
- National Institutes of Health [HL096376, HL097376, HL098174]
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 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 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.
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