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Mitotic regulation of the stability of microtubule plus-end tracking protein EB3 by ubiquitin ligase SIAH-1 and Aurora mitotic kinases.

Microtubule plus-end tracking proteins (+TIPs) control microtubule dynamics in fundamental processes such as cell cycle, intracellular transport, and cell motility, but how +TIPs are regulated during mitosis remains largely unclear. Here we show that the endogenous end-binding protein family EB3 is stable during mitosis, facilitates cell cycle progression at prometaphase, and then is down-regulated during the transition to G(1) phase. The ubiquitin-protein isopeptide ligase SIAH-1 facilitates EB3 polyubiquitination and subsequent proteasome-mediated degradation, whereas SIAH-1 knockdown increases EB3 stability and steady-state levels. Two mitotic kinases, Aurora-A and Aurora-B, phosphorylate endogenous EB3 at Ser-176, and the phosphorylation triggers disruption of the EB3-SIAH-1 complex, resulting in EB3 stabilization during mitosis. Our results provide new insight into a regulatory mechanism of +TIPs in cell cycle transition.

Pubmed ID: 19696028


  • Ban R
  • Matsuzaki H
  • Akashi T
  • Sakashita G
  • Taniguchi H
  • Park SY
  • Tanaka H
  • Furukawa K
  • Urano T


The Journal of biological chemistry

Publication Data

October 9, 2009

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Aurora Kinase B
  • Aurora Kinases
  • COS Cells
  • Cercopithecus aethiops
  • HeLa Cells
  • Humans
  • Isoenzymes
  • Microtubule-Associated Proteins
  • Microtubules
  • Mitosis
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein-Serine-Threonine Kinases
  • RNA, Small Interfering
  • Recombinant Fusion Proteins
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases