TPX2 phosphorylation maintains metaphase spindle length by regulating microtubule flux

Fu, Jingyan; Bian, Minglei; Xin, Guangwei; Deng, Zhaoxuan; Luo, Jia; Guo, Xiao; Chen, Hao; Wang, Yao; Jiang, Qing; Zhang, Chuanmao

doi:10.1083/jcb.201412109

Cited by 57 publications

(53 citation statements)

References 44 publications

(74 reference statements)

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“…The role of TPX2 in spindle assembly and size control is more complicated. Depletion of the TPX2 ortholog D‐TPX2 from Drosophila melanogaster syncytial embryos and S2 cells resulted in spindle shortening (Goshima, ; Hayward & Wakefield, ), and human cells require phosphorylation of TPX2 by Aurora A for normal spindle length (Bird & Hyman, ; Fu et al, ). In contrast, addition of recombinant TPX2 to X. laevis extracts decreased spindle length (Helmke & Heald, ), and we have observed similar effects on X. borealis spindles (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

“…TPX2 also regulates microtubule nucleation in the spindle (Alfaro‐Aco, Thawani, & Petry, ; Petry, ; Petry, Groen, Ishihara, Mitchison, & Vale, ; Scrofani, Sardon, Meunier, & Vernos, ). TPX2 has thus emerged as a central player of spindle assembly and organization in a wide variety of cell types (Fu et al, ; Helmke, Heald, & Wilbur, ; Levy & Heald, ; Ma, Titus, Gable, Ross, & Wadsworth, ) and is overexpressed in many cancers (Chang et al, ; Neumayer, Belzil, Gruss, & Nguyen, ). Our results highlight the importance of TPX2 levels and localization as determinants of meiotic spindle microtubule architecture.…”

Section: Resultsmentioning

confidence: 99%

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Spindle assembly in egg extracts of the Marsabit clawed frog, Xenopus borealis

2018

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Egg extracts of the African clawed frog Xenopus laevis have provided a cell-free system instrumental in elucidating events of the cell cycle, including mechanisms of spindle assembly. Comparison with extracts from the diploid Western clawed frog, Xenopus tropicalis, which is smaller at the organism, cellular and subcellular levels, has enabled the identification of spindle size scaling factors. We set out to characterize the Marsabit clawed frog, Xenopus borealis, which is intermediate in size between the two species, but more recently diverged in evolution from X. laevis than X. tropicalis. X. borealis eggs were slightly smaller than those of X. laevis, and slightly smaller spindles were assembled in egg extracts. Interestingly, microtubule distribution across the length of the X. borealis spindles differed from both X. laevis and X. tropicalis. Extract mixing experiments revealed common scaling phenomena among Xenopus species, while characterization of spindle factors katanin, TPX2, and Ran indicate that X. borealis spindles possess both X. laevis and X. tropicalis features. Thus, X. borealis egg extract provides a third in vitro system to investigate interspecies scaling and spindle morphometric variation.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Spindle assembly in egg extracts of the Marsabit clawed frog, Xenopus borealis

2018

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“…Especially AURKA, TPX2 and DLGAP5 were found to be highly upregulated and correlated with each other. It was shown that during the cell cycle TPX2 and DLGAP5 are phosphorylated by AURKA (15,35). Therefore, a coexpression of AURKA with TPX2 and DLGAP5 seems reasonable.…”

Section: Discussionmentioning

confidence: 99%

AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients

Schneider

Christopoulos

Muley

et al. 2017

International Journal of Oncology

129

120

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The growth of a tumor depends to a certain extent on an increase in mitotic events. Key steps during mitosis are the regulated assembly of the spindle apparatus and the separation of the sister chromatids. The microtubule-associated protein Aurora kinase A phosphorylates DLGAP5 in order to correctly segregate the chromatids. Its activity and recruitment to the spindle apparatus is regulated by TPX2. KIF11 and CKAP5 control the correct arrangement of the microtubules and prevent their degradation. In the present study, we investigated the role of these five molecules in non-small cell lung cancer (NSCLC). We analyzed the expression of the five genes in a large cohort of NSCLC patients (n=362) by quantitative real-time PCR. Each of the genes was highly overexpressed in the tumor tissues compared to corresponding normal lung tissue. The correlation of the expression of the individual genes depended on the histology. An increased expression of AURKA, DLGAP5, TPX2, KIF11 and CKAP5 was associated with poor overall survival (P=0.001–0.065). AURKA was a significant prognostic marker using multivariate analyses (P=0.006). Immunofluorescence studies demonstrated that the five mitosis-associated proteins co-localized with the spindle apparatus during cell division. Taken together, our data demonstrate that the expression of the mitosis-associated genes AURKA, DLGAP5, TPX2, KIF11 and CKAP5 is associated with the prognosis of NSCLC patients.

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“…E The percentage of spindle poles with n centrioles found in cells with multiple c-tubulin foci was assessed (411-805 poles were counted in each group). The significance of TPX2 in mitotic spindle formation, which relies on its interactions with Aurora-A, Eg5, Myo10, and CLASP1, has been extensively studied [22][23][24][25]48]. TPX2 is important for both spindle assembly and spindle pole integrity [16][17][18][19], but the mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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Bipolar spindle assembly is necessary to ensure the proper progression of cell division. Loss of spindle pole integrity leads to multipolar spindles and aberrant chromosomal segregation. However, the mechanism underlying the maintenance of spindle pole integrity remains unclear. In this study, we show that the actin‐binding protein adducin‐1 (ADD1) is phosphorylated at S726 during mitosis. S726‐phosphorylated ADD1 localizes to centrosomes, wherein it organizes into a rosette‐like structure at the pericentriolar material. ADD1 depletion causes centriole splitting and therefore results in multipolar spindles during mitosis, which can be restored by re‐expression of ADD1 and the phosphomimetic S726D mutant but not by the S726A mutant. Moreover, the phosphorylation of ADD1 at S726 is crucial for its interaction with TPX2, which is essential for spindle pole integrity. Together, our findings unveil a novel function of ADD1 in maintaining spindle pole integrity through its interaction with TPX2.

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TPX2 phosphorylation maintains metaphase spindle length by regulating microtubule flux

Abstract: TPX2 is phosphorylated by Aurora A and is essential for normal microtubule flux on the metaphase spindle.

Cited by 57 publications

References 44 publications

Spindle assembly in egg extracts of the Marsabit clawed frog, Xenopus borealis

Spindle assembly in egg extracts of the Marsabit clawed frog, Xenopus borealis

AURKA, DLGAP5, TPX2, KIF11 and CKAP5: Five specific mitosis-associated genes correlate with poor prognosis for non-small cell lung cancer patients

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

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