Distribution of Aurora Kinases

The Distribution of Aurora Kinases Within Cells

The regulatory domain is located in the NH2 terminus of aurora kinases, whereas the catalytic domain is located in the COOH terminus. The catalytic domain, which has a brief piece of varied COOH terminus, has >70% homology with Aurora-A, Aurora-B, and Aurora-C whereas the regulatory domain is mostly different. The Aurora kinases, which are in charge of degradation, have a D-Box in the COOH terminus and an A-Box in the NH2 terminus. The catalytic domain’s threonine site must be phosphorylated for the kinase activity, according to sequence analyses and point mutations.

Recently, the crystal structures of the catalytic domains of Aurora-A and Aurora-B have been determined. The catalytic domain of Aurora kinases, like other serine/threonine protein kinases, is made up of two lobes connected by a hinge. The N lobe is in charge of guiding the ATP phosphate group via a C helix, while the C lobe’s activation loop may accommodate substrates. The Aurora kinases can only carry out their kinase activity when the two lobes reach a certain conformation. The tertiary structural level of the NH2-terminal domain has not yet been investigated.

Despite striking structural and sequence similarities, Aurora kinases have very diverse subcellular distributions. During mitosis, Aurora-A distributes to the pole proximal ends of spindle microtubules and localizes to the pericentriolar material from the conclusion of S phase to the start of the subsequent G1. In contrast, from prometaphase to metaphase, Aurora-B travels to centromeres while staying in the nucleus. After anaphase starts, Aurora-B progressively moves to the midzone and stays there until cytokinesis is finished.

Mitotic control and Aurora Kinases

Due to differing subcellular distributions of the two kinases, Aurora-A and Aurora-B display distinct roles in mitotic regulation. While Aurora-B is involved in chromatin modification, microtubule-kinetochore attachment, spindle checkpoint, and cytokinesis, Aurora-A is primarily engaged in centrosome function, mitotic entrance, and spindle assembly. These processes include these two kinases, as well as other partners and substrates.

Centrosome separation is controlled by Aurora-A

At the G2-M transition, duplicate centriole pairs split and go to the opposite poles of the cell to properly construct a bipolar spindle. There is evidence that functioning Aurora-A is necessary for centrosome separation. Centrosome separation may be prevented in HeLa cells by RNA interference or by microinjecting Aurora-A antibody. Centrosome segregation and spindle formation in C. elegans embryos might be interfered with by knocking down Aurora-A using RNA interference. A monopolar spindle is produced in Xenopus by a dominant-negative Aurora-A mutation, a condition that is comparable to the suppression of the kinesin-related protein XlEg5. It’s probable that Xenopus Aurora-A controls centrosome separation by phosphorylating the kinesin-related proteins since XlEg5 is phosphorylated by the protein both in vivo and in vitro.

Chromatid separation is controlled by Aurora-B

Each kinetochore must be connected to microtubules from the opposing poles in order to properly separate the chromatids. The spindle checkpoint and the repair of incorrect attachment are the two methods that cells have developed to control this process. It has long been assumed that Aurora-B is essential for both routes since Aurora-B inhibition results in a greater frequency of syntenic and/or merotelic attachments in cells during prometaphase and leads these cells to reach anaphase without arrest and with misaligned chromosomes.