4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1

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

Research output: Contribution to journalArticle

29 Scopus citations

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 mitosis. 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 multipolar 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.

Original languageEnglish (US)
Pages (from-to)3463-3471
Number of pages9
JournalCell Cycle
Volume11
Issue number18
DOIs
StatePublished - Sep 15 2012

Keywords

  • 4E-BP1
  • Cell cycle
  • Centrosome
  • Genomic stability
  • PLK1
  • Spindle

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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  • Cite this

    Shang, Z. F., Yu, L., Li, B., Tu, W. Z., Wang, Y., Liu, X. D., Guan, H., Huang, B., Rang, W. Q., & Zhou, P. K. (2012). 4E-BP1 participates in maintaining spindle integrity and genomic stability via interacting with PLK1. Cell Cycle, 11(18), 3463-3471. https://doi.org/10.4161/cc.21770