Given that cellular division is one of the defining characteristics of living things, it is not unexpected that a huge number of proteins closely regulate this process. Among this network of regulatory proteins, Aurora kinases are particularly important because they regulate the segregation of chromatids, which is a critical step in cellular division. Genetic instability, a condition connected to cancer, is brought on by errors in chromatid segregation. Aurora The chromosomal location 20q13, which is often seen in human breast cancers, has a gene.
While Aurora C expression contributes to spermatogenesis at the time when cells assemble the two meiotic spindles and also works in conjunction with Aurora B to control mitotic chromosome dynamics in mammalian cells, Aurora B is a chromosome passenger involved in cytokinesis and chromosome architecture. A 290-amino-acid protein encoded by a unique human Aurora C splicing variant (Aurora C-SV) has recently been cloned and described.
Only the Aurora A and B kinases are known to exist in other metazoans, such as the frog, fruit fly, and worm, whereas the three Aurora kinases—Aurora A, Aurora B, and Aurora C—are uniquely encoded for in the genomes of mammals. Only one Aurora-like homolog is encoded by the yeast genomes S. cerevisiae and S. pombe, indicating that the roles of auroras have changed over time.
The three vertebrate Auroras appear to have all descended from a single urochordate progenitor, according to evolutionary trees. In cold-blooded vertebrates and mammals, Aurora A is an orthologous lineage, but structurally related Auroras B and C emerged more recently in mammals from a duplication of an ancestral Aurora B/C gene discovered in cold-blooded vertebrates.
Human Auroras A–C are kinases that range in size from 309 to 403 amino acids and have a rather high degree of interspecies sequence divergence. The total sequence similarity between human and rodent proteins, for instance, is 82% for Aurora A, 84% for Aurora B, and 78% for Aurora C. The N-terminal domain of Aurora kinases A through C, which ranges in length from 39 to 129 residues, the protein kinase domain, and the brief C-terminal domain, which is just 15-20 residues long, are organized similarly.
Creation and destruction
Human The route consisting of the anaphase promoting complex/cyclosome (APC/C), ubiquitin, and proteasome is used to turn over Aurora A.. Aurora According to Taguchi et al. (2002), a degradation depends on hCdh1 in vivo rather than hCdc20 and includes two separate degradation motifs. The first one is a D-Box-activating N-terminal motif (RxLxPS). This pattern gives a second motif, a D-Box, made out of the letters RxxLxxG, functionality.
For mitosis to proceed properly, a functional equilibrium between Aurora A and mitotic checkpoint proteins must be maintained. When Aurora A is overexpressed, it interferes with the normal assembly of the mitotic checkpoint complex at the level of the Cdc20-BubR1 interaction, causing genomic instability and cancer. In human cancer cell lines, its overexpression results in resistance to taxol-induced apoptosis.
Potential uses in medicine
A reliable indicator of tumor development and prognosis is Aurora A. Therefore, reducing its kinase activity may aid in lessening tumor aggressiveness. The catalytic domain of human Aurora A has a similar architecture to that seen in many kinases, according to the crystal structure, although 3 out of 26 residues bordering its ATP-binding active site are variable. Additionally, Aurora A exhibits distinct properties in its fluoro-phenyl pocket and activation loop area.
Helpful Note: If that’s your theory, you may go through the library of potentially selective Aurora A kinase inhibitors in the Chemdiv Compound Collection. The aurora libraries might include up to 10,000 different compounds.