Aurora A kinase and its substrate TACC3 are required for central spindle assembly

Abstract

Cell division entails a marked reorganization of the microtubule network to form the spindle, a molecular machine that ensures accurate chromosome segregation to the daughter cells. Spindle organization is highly dynamic throughout mitosis and requires the activity of several kinases and complex regulatory mechanisms. Aurora A (AurA) kinase is essential for the assembly of the metaphase bipolar spindle and, thus, it has been difficult to address its function during the last phases of mitosis. Here, we examine the consequences of inhibiting AurA in cells undergoing anaphase, and show that AurA kinase activity is necessary for the assembly of a robust central spindle during anaphase. We also identify TACC3 as an AurA substrate essential in central spindle formation.

Suppression of centrosome protein TACC3 induces G1 arrest and cell death through activation of p38–p53–p21 stress signaling pathway

“…Our findings demonstrate that loss of TACC3, which is a centrosomal and cancer-associated adaptor protein (Kinoshita et al, 2005;Lioutas and Vernos, 2013;Yao et al, 2007), results in a centrosome-mediated cellular response that leads to G1 arrest and cell death. These results can be linked to earlier studies showing that centrosome defects interfere with cellular signaling pathways, which in turn trigger a stress response (Srsen et al, 2006;Mikule et al, 2007).…”

Opposing roles for JNK and Aurora A in regulating WD40-Repeat Protein 62 association with spindle microtubules

“…AURKA is a centrosome-and spindle-associated mitotic kinase with well-defined functions during early mitotic phases, including regulation of centrosome maturation and separation, mitotic entry and bipolar spindle assembly (Barr and Gergely, 2007;Nikonova et al, 2013). Recent studies have also revealed important roles in central spindle assembly in late mitotic stages and during interphase (Lioutas and Vernos, 2013;Nikonova et al, 2013;Reboutier et al, 2013). The expression of AURKA is upregulated in G2 and its activity is increased through interactions with protein activators and by kinase autophosphorylation primarily to facilitate mitotic entry (Bayliss et al, 2003;.…”

TACC3 Protein Regulates Microtubule Nucleation by Affecting γ-Tubulin Ring Complexes

“…In human cells, TACC3 has been shown to be associated with the organization of the mitotic spindle poles (32). Subsequent studies revealed that TACC3 depletion induced chromosomal misalignment, reduced spindle stability, and triggered apoptosis in cells (33)(34)(35). However, the mechanism by which TACC3 regulates microtubule functions at the microtubule-organizing center (MTOC) has not been described.…”