Abstract
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.
Highlights
Microtubule dynamics are essential in many cellular processes, including cell motility, intracellular transport, accurate mitosis, and cytokinesis in all eukaryotes
We report that the E3 SIAH-1 interacts with EB3 and mediates EB3 polyubiquitination and degradation through the ubiquitin-proteasome system
Recent publications provide a molecular basis of the recognition/specificity as the hydrophobic interaction between SIAH-1 and its substrates [45, 47]
Summary
Microtubule dynamics are essential in many cellular processes, including cell motility, intracellular transport, accurate mitosis, and cytokinesis in all eukaryotes. We show that the endogenous end-binding protein family EB3 is stable during mitosis, facilitates cell cycle progression at prometaphase, and is down-regulated during the transition to G1 phase.
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