The three Aurora-A, B, and C mitotic protein kinases are complementary enzymes that control several mitotic processes. The many kinases must be locally engaged for this to happen, and mitosis carefully controls the timing and location of this activity.
For instance, Aurora-B is active in the nucleus, then at chromosomal kinetochores, and finally one at the midbody. Aurora-A is initially active at the centrosomes, followed by activity on microtubules at the spindle pole. By locally binding to regulators, aurora kinase activity is controlled in both location and time.
To become active, aurora kinases require protein partners. For example, Aurora-A binds to the Xenopus kinesin-like protein 2 targeting protein (TPX2) and is triggered at the spindle pole, whereas Aurora-B and Aurora-C bind to the INner ChROMosome Protein (INCENP) and are active on the chromosomes. These activations include the kinase’s T-threonine loop’s residue being autophosphorylated. Different strategies are employed by other protein partners to activate Auroras.
These enable the kinase to be activated at various times and places inside the cell. The list of regulators for Aurora kinases in this review is current. The existence of an active Aurora kinase is explained by the subcellular location of these regulators.
It also explains the variations in Aurora kinase activity localizations seen during mitosis’ cell cycle advancement. Recent information suggests that aurora kinases are involved in nonmitotic activities, hence it is important to identify their activators in these processes.
The two primary stages of cell division are interphase and mitosis, which are followed by the physical separation of the two daughter cells. The cell doubles the components that will be divided into two daughter cells during mitosis during interphase. Human cells go through the entire process in roughly 24 hours, even though mitosis only lasts an hour.
Phosphorylation and dephosphorylation processes play a major role in controlling this brief period. Cyclin-dependent kinase 1 (CDK1), polo-like kinase 1 (Plk1), NIMA-related kinase 2 (Nek2), and the Aurora kinases (Aurora-A, B, and C) are some of the important protein kinases involved. The three Aurora-A, B, and C mitotic protein kinases are complementary enzymes that control several mitotic processes.
Since their identification, Aurora kinases have gained importance as potential targets for the creation of cancer therapy inhibitors. However, the many ways in which they are regulated make it more challenging to create effective medications that target the kinases. A nonexhaustive list of posttranslational modifications (PTMs) that impact how the kinases operate is often reported in this study.
These PTMs can be employed as biomarkers, similar to the test now under debate that measures the kinase activity in vivo by phosphorylating T288 in Aurora-A. What’s more intriguing is that these PTMs may be employed to create unique inhibitory tactics that don’t focus on the kinase active site.
For example, the binding of TPX2 to Aurora-A has been targeted in the hunt for Aurora-A inhibitors. This type of PTM-targeting strategy offers several opportunities for the targeted suppression of Aurora kinases. The ensuing years should see the discovery of several novel inhibitors.
Read: According to that supposition, you may search the Chemdiv Compound Collection’s library of possibly selective Aurora A kinase inhibitors here. There are almost 10,000 distinct compounds in the aurora libraries.