4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1
Volume 11, Issue 18
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September 15, 2012
Pages 3463 - 3471http://dx.doi.org/10.4161/cc.21770
: 4E-BP1, PLK1, cell cycle, centrosome, genomic stability, spindle
Authors: Zeng-Fu Shang, Lan Yu, Bing Li, Wen-Zhi Tu, Yu Wang, Xiao-Dan Liu, Hua Guan, Bo Huang, Wei-Qing Rang and Ping-Kun Zhou View affiliations
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.
Received: April 1, 2012; Accepted: August 8, 2012; Published Online: August 23, 2012
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