Aurora kinases are a family of proteins known as serine/threonine kinases, which are enzymes that add phosphate groups to other proteins. These proteins are fundamental for cell proliferation, the process of cell growth and division. They play a significant role in ensuring the precise distribution of genetic material during cell division.
Aurora Kinases in Cell Division
Aurora kinases are involved in cell division, ensuring a cell’s genetic material is accurately distributed into two daughter cells. This is accomplished by three classes of aurora kinases: Aurora A, Aurora B, and Aurora C. Their activities are regulated throughout the cell cycle to prevent errors.
Aurora A is active during early mitosis, in prophase. It is responsible for the duplication and separation of centrosomes, the main microtubule-organizing centers. Aurora A also helps in the assembly and stability of the mitotic spindle, which pulls chromosomes apart. Its activity is highest during the G2 to M phase transition, preparing the cell for division.
Aurora B functions in the attachment of the mitotic spindle to the centromere on each chromosome. It is a component of the chromosomal passenger complex, which moves along chromosomes during cell division. Aurora B helps regulate chromosome segregation and cytokinesis, where the cell physically divides.
Aurora C’s function is primarily observed in germ-line cells. It is also considered a chromosomal passenger protein. Like Aurora B, Aurora C is involved in chromosome binding to kinetochores and chromosome segregation, ensuring accurate distribution of genetic material in these cells.
How Aurora Kinases Contribute to Cancer
When aurora kinases malfunction, they can lead to genetic instability. This instability arises from errors in chromosome segregation, leading to aneuploidy, where daughter cells receive an incorrect number of chromosomes. Such errors can disrupt normal cellular processes and contribute to cancer development.
Overexpression or increased activity can lead to mitotic abnormalities. Excess activity can cause cells to divide uncontrollably, bypassing checkpoints that prevent damaged cells from proliferating. This uncontrolled cell growth is a hallmark of cancer, as mutated cells multiply without restraint. Improper distribution of genetic information during cell division generates aneuploid cells, a common feature in many cancerous tumors.
Defects in aurora kinase activity can also promote cancer. Problems with centrosome maturation or spindle assembly can result in faulty cell division, creating cells with an abnormal number of chromosomes. Such genomic instability allows further mutations to accumulate, driving tumor progression. The accumulation of these errors can lead to uncontrolled proliferation and survival of cancer cells.
Aurora Kinases as Cancer Treatment Targets
Given their involvement in cell division and cancer, aurora kinases are promising targets for cancer therapy. The strategy involves developing specific inhibitors that interfere with kinase activity, disrupting uncontrolled cancer cell growth. This approach aims to halt cancer progression by restoring control over cell division.
Scientists create molecules that block aurora kinase activity, preventing their functions in cell division. Inhibiting these proteins aims to induce mitotic arrest, preventing cancer cells from completing division, or to promote programmed cell death (apoptosis). This targeted intervention affects rapidly dividing cancer cells while minimizing harm to healthy cells.
Numerous aurora kinase inhibitors are being explored for treating various cancers. These inhibitors bind to aurora kinase enzymes, preventing them from phosphorylating target proteins necessary for cell division. This interference can lead to mitotic delays, polyploidy (cells with more than two sets of chromosomes), and cancer cell death. The development of these inhibitors represents a significant area of oncology research, leveraging the understanding of aurora kinase biology for therapeutic benefit.