The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme?
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.
Asteriti
Italia Anna
IA
Institute of Molecular Biology and Pathology, CNR, c/o Sapienza University of Rome, Via degli Apuli 4, 00185 Rome, Italy.
Rensen
Wilhelmina Maria
WM
Lindon
Catherine
C
Lavia
Patrizia
P
Guarguaglini
Giulia
G
D000818:Animals; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D020035:Holoenzymes / Q000502:physiology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D008938:Mitosis; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009857:Oncogenes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D020035:Holoenzymes; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases