The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme?

Biochim Biophys Acta. 2010 Dec;1806(2):230-9. doi: 10.1016/j.bbcan.2010.08.001. Epub 2010 Aug 12.

Abstract

The Aurora-A kinase regulates cell division by phosphorylating multiple downstream targets in the mitotic apparatus. Aurora-A is frequently overexpressed in tumor cells and it is therefore regarded as a novel candidate target in anti-cancer therapy. Its actual contribution to cell transformation, however, is not entirely clarified; furthermore, its transforming ability has been found to vary broadly depending on the systems and experimental conditions in which it was assayed. This variability suggests that Aurora-A overexpression requires the concomitant deregulation of partner factor(s) to fully elicit its oncogenic potential. Molecular and structural studies indicate that the full activation and correct mitotic localisation of Aurora-A require its interaction with the spindle regulator TPX2. In this review we propose a brief reappraisal of Aurora-A intrinsic oncogenic features. We then present literature screening data indicating that TPX2 is also overexpressed in many tumor types, and, furthermore, that Aurora-A and TPX2 are frequently co-overexpressed. We therefore propose that the association of Aurora-A and TPX2 gives rise to a novel functional unit with oncogenic properties. We also suggest that some of the roles that are conventionally attributed to Aurora-A in cell transformation and tumorigenesis could in fact be a consequence of the oncogenic activation of this unit.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Holoenzymes / physiology*
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / physiology*
  • Mitosis
  • Neoplasms / enzymology
  • Neoplasms / etiology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Oncogenes
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Cell Cycle Proteins
  • Holoenzymes
  • Microtubule-Associated Proteins
  • Nuclear Proteins
  • TPX2 protein, human
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases