Posted by: Dan | August 30, 2007

Aurora-A Kinase as a Mitotic Centrosomal Kinase

A week ago, I mentioned Plk4 as a kinase implicated in centrosome duplication. An array of other factors appear to be involved in centrosome duplication and spindle pole assembly as well.

Case in point, Aurora-A kinase, as reviewed in JCS by Barr and Gergely (2007) [additional citations in original]:

Centrosomes consist of a pair of centrioles surrounded by a pericentriolar matrix (PCM), the site of microtubule (MT) assembly. To form the poles of the bipolar spindle, centrosomes must undergo a series of tightly controlled events including duplication, separation and maturation (for reviews, see Nigg, 2007; Azimzadeh and Bornens, 2007). Loss-of-function studies established some time ago that Aurora-A is required for multiple steps during mitosis. Perturbing Aurora-A leads to defective centrosome separation and maturation in a wide variety of experimental model systems. Cell cycle progression, mitotic spindle pole organisation and MT stability are also often compromised in the absence of Aurora-A.

The expression and localisation of Aurora-A is consistent with its function as a mitotic centrosomal kinase. During G1/S phase, its levels are low, but, in G2 phase, the levels of Aurora-A mRNA and protein kinase activity all rise rapidly, reaching a peak in early mitosis. The cdh1-activated anaphase-promoting complex/cyclosome (APC) initiates Aurora-A degradation in anaphase B but only completes it in G1 phase. Aurora-A kinase is present on duplicated centrosomes from late S phase until early G1 phase and it is also detectable on spindle MTs during mitosis. The rapid turnover of Aurora-A both in the centrosome and on the mitotic spindle argues for a signalling rather than a structural role for the kinase at these locations. This is not surprising, because as well as playing a significant role in organising the mitotic MT network, the centrosome also acts as an important signalling platform. Thus the Aurora-A kinase at the centrosome is clearly in prime position to coordinate mitotic events.

So while Plk4 appears to be involved in the actual duplication event and biogenesis of new daughter centrioles, Aurora-A appears to be involved in separation of the twin centrioles to establish the spindle poles for chromosome segregation.

  • Barr AR, Gergely F. Aurora-A: the maker and breaker of spindle poles. J Cell Sci. 2007 Sep 1;120(Pt 17):2987-96.
  • Nigg, E. A. Centrosome duplication: of rules and licenses. Trends Cell Biol. 2007 May; 17:215-221.
  • Azimzadeh, J. and Bornens, M. Structure and duplication of the centrosome. J. Cell Sci. 2007 Jul 1;120(Pt 13):2139-42.

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