Eg5KIF11

Eg5KIF11, commonly known as KIF11 or kinesin-5 family member 11, is a conserved microtubule motor protein of the kinesin superfamily. It plays a central role in mitosis by driving the separation of duplicated centrosomes and the assembly of the bipolar mitotic spindle, enabling proper chromosome segregation in proliferating cells.

Structurally, Eg5KIF11 contains an N-terminal motor domain with ATPase activity, a central coiled-coil stalk, and a C-terminal microtubule-binding region. It forms dimers that assemble into bipolar tetramers capable of crosslinking anti-parallel microtubules and sliding them apart. This activity generates outward forces that push the two spindle poles away from each other at the onset of mitosis, facilitating spindle bipolarity.

In cells, Eg5KIF11 localizes to spindle microtubules during mitosis and is essential for forming a functional bipolar spindle, proper chromosome alignment, and timely progression through mitosis. Its activity is regulated by cell-cycle cues and post-translational modifications that modulate motor activity and localization.

Because of its indispensable role in mitotic spindle assembly, Eg5KIF11 is a well-studied target for anti-cancer therapies. Small-molecule inhibitors, beginning with monastrol and progressing to later compounds such as ispinesib and filanesib, block kinesin-5 motility and trap cells in a mitotic arrest with aberrant or monopolar spindles. While these inhibitors demonstrated anti-tumor activity in preclinical models, clinical development has faced challenges related to toxicity and therapeutic window. Ongoing research explores combination strategies and tumor-specific dependencies to harness Eg5KIF11 inhibition more effectively.