Eg5

Eg5, or kinesin-5 family member 11 (KIF11), is a mitotic motor protein found in many eukaryotes. It is a member of the kinesin-5 family and functions as a plus-end directed microtubule motor that forms a homotetramer, with motor domains at opposite ends, enabling it to crosslink and slide antiparallel microtubules.

In the mitotic spindle, Eg5 drives the separation of spindle poles to establish a bipolar spindle, a critical step for correct chromosome alignment and segregation. The motor uses ATP hydrolysis to generate outward forces that slide overlapping antiparallel microtubules apart, pushing the two poles toward opposite ends of the cell. Through its activity, Eg5 helps create the force balance required for spindle integrity during early mitosis.

Eg5 localizes to spindle microtubules from prophase through metaphase and its activity is tightly regulated by phosphorylation and interaction with other spindle components, including TPX2 and dynein-family motors. Its function is essential for proper mitosis in many cell types; loss or inhibition of Eg5 disrupts bipolar spindle formation and activates the spindle assembly checkpoint, leading to mitotic arrest.

Clinically, Eg5 has been a target of anti-mitotic cancer therapies. First-in-class inhibitors such as monastrol demonstrated that selective Eg5 blockade can induce monopolar spindles. Since then, several small-molecule Eg5 inhibitors (for example ispinesib and filanesib) have entered preclinical and clinical testing. Results have shown activity in some contexts but have often been limited by toxicity and modest single-agent efficacy, prompting ongoing research into combination strategies and patient selection.