TPX2 regulates the localization and activity of Eg5 in the mammalian mitotic spindle

Abstract

TPX2 promotes mitotic spindle formation by enhancing Eg5 accumulation on microtubules and limiting motor activity.

APC/C is an essential regulator of centrosome clustering

“…2d). In addition, cells where Eg5 is overactive often undergo multipolar mitosis 18 . Second, Eg5 carries several putative KEN 19 and D-box 20 motifs at the C-terminal.…”

“…Here we show that Eg5 stabilization by selective inhibition of APC/C-CDH1 is sufficient to kill CA cells, suggesting that selective targeting of APC/C-CDH1 may represent an effective therapeutic approach in CA tumours. In addition, it has been shown that TPX2 acts as a brake on Eg5 motor, and that knockdown of TPX2 results in increased Eg5 activity and multipolar spindles in cancer cells 18 . It is plausible that any therapeutic approach aimed to increase outward forces on the mitotic spindle could effectively kill tumours with CA.…”

Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes

“…In somatic cells (Ma et al, 2011), upon binding a microtubule-binding protein called TPX2, AURKA auto-activates and regulates the building of the bipolar spindle by recruiting other PCM proteins, promoting microtubule nucleation and anti-parallel sliding forces, and maintaining the integrity of astral microtubules with the cortex (Dodson and Bayliss, 2012;Giubettini et al, 2011;Kufer et al, 2002;Li et al, 2008;Scrofani et al, 2015). In mouse oocytes, overexpression of AURKA increases MTOC numbers prematurely (Saskova et al, 2008;Solc et al, 2012), and its depletion causes disorganized meiosis I spindles (Saskova et al, 2008).…”

Adducin‐1 is essential for spindle pole integrity through its interaction with TPX2

“…Our results indicated that while the interaction of TPX2 with Aurora‐A is crucial for controlling spindle length (Fig 5), the interactions of TPX2 with ADD1 and Eg5 are essential for spindle pole integrity (Figs 5 and 6). TPX2 has been shown to bind Eg5 and suppress its motor activity during mitosis, which ensures proper bipolar spindle formation 25. Interestingly, we found that the multipolar spindles and centriole splitting induced by ADD1 depletion were Eg5‐dependent (Fig 7), rendering it possible that ADD1 binding may be necessary for TPX2 to interact with Eg5 and/or suppress Eg5 activity.…”