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Gene Review

tpx2-a  -  TPX2, microtubule-associated

Xenopus laevis

Synonyms: dil-2, dil2, hctp4, repp86, tpx2
 
 
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High impact information on TPX2

 

Biological context of TPX2

  • TPX2 has multiple functions during mitosis, including microtubule nucleation around the chromosomes and the targeting of Xklp2 and Aurora A to the spindle [3].
  • This interaction causes TPX2 to stimulate both the phosphorylation and the kinase activity of Eg2 in a microtubule-dependent manner [1].
  • TPX2-depleted nuclei assemble nuclear envelopes, nuclear pore complexes, and a lamina, and they perform nuclear-specific functions, including DNA replication [2].
  • Our finding that a known binding protein, and not a conventional protein kinase, is the relevant activator for Aurora A suggests a biochemical model in which the dynamic localization of TPX2 on mitotic structures directly modulates the activity of Aurora A for spindle assembly [4].
  • One such protein is TPX2, a required spindle assembly factor in higher eukaryotes whose ability to activate Aurora A by direct binding to the kinase catalytic domain has been established by biochemical and structural analysis [5].
 

Anatomical context of TPX2

  • These and previous results suggest that under physiological conditions, TPX2 is essential for microtubule nucleation around chromatin and functions in a network of other molecules, some of which also are regulated by RanGTP [3].
 

Associations of TPX2 with chemical compounds

  • We have performed a detailed domain functional analysis of TPX2 and found that a large N-terminal domain containing the Aurora A binding peptide interacts directly with and nucleates microtubules in pure tubulin solutions [3].
 

Enzymatic interactions of TPX2

  • Remarkably, Aurora A that has been fully deactivated by Protein Phosphatase 2A (PP2A) becomes phosphorylated and reactivated by recombinant TPX2 in an ATP-dependent manner [4].

References

  1. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Tsai, M.Y., Wiese, C., Cao, K., Martin, O., Donovan, P., Ruderman, J., Prigent, C., Zheng, Y. Nat. Cell Biol. (2003) [Pubmed]
  2. TPX2 is required for postmitotic nuclear assembly in cell-free Xenopus laevis egg extracts. O'Brien, L.L., Wiese, C. J. Cell Biol. (2006) [Pubmed]
  3. Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Brunet, S., Sardon, T., Zimmerman, T., Wittmann, T., Pepperkok, R., Karsenti, E., Vernos, I. Mol. Biol. Cell (2004) [Pubmed]
  4. A novel mechanism for activation of the protein kinase Aurora A. Eyers, P.A., Erikson, E., Chen, L.G., Maller, J.L. Curr. Biol. (2003) [Pubmed]
  5. Regulation of Xenopus Aurora A activation by TPX2. Eyers, P.A., Maller, J.L. J. Biol. Chem. (2004) [Pubmed]
 
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