KIF18A, or kinesin family member 18A, is a protein in human cells that plays a role in cellular mechanics, particularly in how cells organize and divide. Understanding its activities is important for comprehending cell biology.
What KIF18A Is
KIF18A belongs to a group of proteins known as kinesin motor proteins. These “molecular motors” generate movement within cells by moving along specific cellular tracks called microtubules, which are part of the cell’s internal skeleton. KIF18A is found associated with microtubules, particularly within the cytoplasm and at structures like the kinetochore and mitotic spindle.
The protein is composed of 898 amino acids, with a molecular mass of approximately 102 kilodaltons. Its structure allows it to bind to microtubules and use energy from ATP hydrolysis to “walk” along them, facilitating cellular transport and organizational tasks.
KIF18A’s Function in Cell Division
KIF18A’s primary function is in mitosis, the process where a single cell divides into two identical daughter cells. During mitosis, it plays a role in chromosome segregation and the organization of the spindle, a microtubule structure that separates chromosomes. KIF18A is a plus-end directed motor protein, moving towards the growing ends of microtubules. It accumulates at the plus ends of spindle microtubules during prophase and metaphase, with levels decreasing during anaphase.
KIF18A regulates the length and stability of kinetochore microtubules, which attach to chromosomes. By reducing chromosome oscillations before anaphase and slowing their movement towards the poles, KIF18A helps ensure chromosomes align properly at the metaphase plate. This contributes to accurate chromosome congression. It also stabilizes the CENPE-BUB1B protein complex at kinetochores during early mitosis, which aids chromosome alignment.
KIF18A’s Role in Disease
Dysregulation or abnormal levels of KIF18A are linked to various diseases, particularly cancer. Altered KIF18A activity can lead to errors in chromosome segregation, a common characteristic of cancer cells. When KIF18A is overexpressed or mutated, it can disrupt the precise chromosome separation needed for healthy cell division. This can result in aneuploidy, a condition where cells have an abnormal number of chromosomes.
KIF18A is overexpressed in several human cancers, including breast, lung, and colorectal cancer. This overexpression can contribute to uncontrolled tumor growth and progression by promoting genomic instability. For instance, increased KIF18A activity has been associated with higher tumor stages and increased cell proliferation in prostate cancer. Abnormal KIF18A levels can indicate disease progression and aggressive tumor behavior.
KIF18A as a Drug Target
Understanding KIF18A’s role in uncontrolled cell division has led to research into targeting it for cancer treatment. Inhibiting KIF18A in cancer cells aims to disrupt their abnormal cell division and potentially induce cell death. By interfering with KIF18A’s ability to regulate microtubule dynamics and chromosome segregation, researchers seek to halt the proliferation of cancerous cells.
Developing KIF18A inhibitors is a strategy for targeted therapy, aiming to specifically attack cancer cells while minimizing harm to healthy cells. This approach could offer more precise treatments with fewer side effects compared to traditional chemotherapy, which often affects all rapidly dividing cells. While challenges remain in developing highly selective and potent KIF18A-targeting drugs, ongoing research explores compounds that can block its activity.