Aurora kinases

Hello friends, Let's talk about Aurora kinases today.... Aurora sounds so beautiful, right ?

Aurora kinases represent serine threonine kinases with instrumental role in cell division.

Specifically, Aurora kinase A is required for duplication and separation of centromere, and Aurora B is required for attachment of microtubules to centromere.

They are often over expressed in tumors resulting in defective cytokinesis during cell division, eventually causing aneuploidy and driving the carcinogenesis.

Now, it really gets interesting; usually when functioning of microtubules are perturbed say by paclitaxel, then spindle check point inhibitor is activated leading to cell demise by upregulation of P53, PUMA and other mediators.

But in case of Aurora kinase inhibition, cells keep on dividing especially in case of P53 mutated cells. Since centromeres will not segregate, it ultimately leads to tetraploid genome and four centromeres in a cell, causing catastrophic mitosis in subsequent cell cycle effectively tearing apart the genome.

They are significant because often when other tyrosine kinase inhibitors targeting EGFR, VEGFR, FGFR are used, tumors over express Aurora kinases, there by over riding the inhibition mediated by tyrosine kinase inhibitors.... So targeting them is key to maintain remission in patients already on kinase inhibitors.

Few examples of drugs in trials: Monastrol, Hesperidin.

It's called Aurora because of the similarity between the appearance of microtubule spindles during cell division and Aurora Borealis.

Pretty Majestic, right?

Submitted by Kirtan Patolia