4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1 |
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| Authors: | Zeng-Fu Shang Lan Yu Bing Li Wen-Zhi Tu Yu Wang Xiao-Dan Liu Hua Guan Bo Huang Wei-Qing Rang Ping-Kun Zhou |
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| Institution: | 1.Department of Radiation Toxicology and Oncology; Beijing Institute of Radiation Medicine; Beijing, PR China;2.Division of Molecular Radiation Biology; Department of Radiation Oncology; University of Texas Southwestern Medical Center at Dallas; Dallas, TX USA;3.Institute for Environmental Medicine and Radiation Hygiene; The College of Public Health; University of South China; Hengyang, PR China |
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| Abstract: | The essential function of eIF4E-binding protein 1 (4E-BP1) in translation initiation has been well established; however, the role of 4E-BP1 in normal cell cycle progression is coming to attention. Here, we revealed the role of 4E-BP1 on mitotic regulation and chromosomal DNA dynamics during mitosis. First, we have observed the co-localization of the phosphorylated 4E-BP1 at T37/46 with Polo-like kinase 1 (PLK1) at the centrosomes during. Depression of 4E-BP1 by small interfering RNA in HepG2 or HeLa cells resulted in an increased outcome of polyploidy and aberrant mitosis, including chromosomal DNA misaligned and multi-polar spindles or multiple centrosomes. We observed that 4E-BP1 interacted with PLK1 directly in vitro and in vivo in mitotic cells, and the C-terminal aa 77–118 of 4E-BP1 mediates its interaction with PLK1. PLK1 can phosphorylate 4E-BP1 in vitro. Furthermore, the depletion of 4E-BP1 sensitized HepG2 and HeLa cells to the microtubule disruption agent paclitaxel. These results demonstrate that 4E-BP1, beyond its role in translation regulation, can function as a regulator of mitosis via interacting with PLK1, and possibly plays a role in genomic stability maintaining. |
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| Keywords: | 4E-BP1 PLK1 cell cycle centrosome genomic stability spindle |
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