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.
Mesh Terms:
Amino Acid Sequence, Animals, 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
J. Biol. Chem.
Date: Oct. 09, 2009
Download Curated Data For This Publication
145760
Switch View:
  • Interactions 13