4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1.
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.
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, PR China.
Zeng-Fu
ZF
Shang
Lan
L
Yu
Bing
B
Li
Wen-Zhi
WZ
Tu
Yu
Y
Wang
Xiao-Dan
XD
Liu
Hua
H
Guan
Bo
B
Huang
Wei-Qing
WQ
Rang
Ping-Kun
PK
Zhou
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D042822:Genomic Instability / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011123:Polyploidy; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D017239:Paclitaxel; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C087000:EIF4EBP1 protein, human