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 RIS Download
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