Kinesin family member 11 (KIF11) (KSP)

Kinesin family member 11 (KIF11), also known as Kinesin Spindle Protein (KSP) or Eg5, is a plus-end-directed motor protein belonging to the kinesin-5 subfamily that is essential for establishing and maintaining the bipolar mitotic spindle (NIH, 1.1.1; Wikipedia, 1.2.2). It functions as a homotetramer that cross-links and slides anti-parallel microtubules, a process required for centrosome separation and chromosome alignment during mitosis (NIH, 1.3.1; GeneCards, 1.2.1). KIF11 is overexpressed in numerous cancers, including lung, breast, and pancreatic cancer, where it promotes uncontrolled cell proliferation and is associated with poor prognosis (NIH, 1.1.1, 1.3.3). As a therapeutic target, KIF11 inhibitors like ispinesib and filanesib aim to induce mitotic arrest and apoptosis by causing the formation of monoastral spindles (NIH, 1.4.4; ResearchGate, 1.1.4). Unlike traditional microtubule-targeting agents, KIF11 inhibitors are generally not associated with peripheral neuropathy because the protein is not expressed in adult neurons (NIH, 1.1.1, 1.3.3). However, clinical development has been hindered by dose-limiting toxicities such as neutropenia and limited efficacy in solid tumors (NIH, 1.4.4; ResearchGate, 1.3.5). Mutations in the KIF11 gene are also linked to a developmental syndrome involving microcephaly, lymphedema, and chorioretinopathy (GeneCards, 1.2.1; NIH, 1.4.1).

Other names

Eg5Kinesin spindle proteinKinesin-5BimCHKSPKNSL1MCLMRTRIP5

Allosteric inhibition of the motor domain (typically at the L5 loop or α4/α6 pocket), which inhibits ATPase activity and prevents the separation of duplicated centrosomes, leading to the formation of monoastral spindles, mitotic arrest, and subsequent apoptosis (NIH, 1.1.1, 1.4.4).