Highly Expressed in Cancer 1 and NIMA Related Kinase 2 protein-protein interaction (Hec1/NEK2 (sometimes also written as HEC1/NEK2))

The interaction between Highly Expressed in Cancer 1 (Hec1, also known as NDC80) and NIMA Related Kinase 2 (NEK2) forms a critical protein-protein interface essential for accurate mitotic spindle checkpoint function, kinetochore attachment, and chromosome segregation during cell division. Hec1 itself does not have enzymatic activity but is a component of the Ndc80 kinetochore complex; NEK2 is a serine/threonine kinase regulating centrosome separation and kinetochore dynamics. Disruption of the Hec1/NEK2 interaction by targeted small molecules like INH1 or TH-39 causes NEK2 degradation, mitotic arrest, and apoptosis, suppressing proliferation in cancer cells. Overexpression of Hec1 and NEK2 is frequent in aggressive cancers and is associated with drug resistance and poor prognosis, establishing their interaction as a rational therapeutic target in oncology[1][2][3][4][5][6].

Other names

Hec1 (also NDC80)NEK2NDC80/NEK2 interactionHec1-Nek2 interaction

Small molecules that disrupt the Hec1/NEK2 interaction induce cell cycle arrest and apoptosis in cancer cells by triggering NEK2 degradation and loss of mitotic control. Death-trap mechanism: Binding of inhibitor to Hec1 leads to Nek2 degradation. Induction of cell cycle arrest (G0/G1 or G2/M). Apoptosis through disruption of spindle checkpoint.