Hec1

Hec1, also known as NDC80, is a conserved kinetochore protein that forms the core NDC80 complex with NUF2, SPC24, and SPC25. It is a key component of the outer kinetochore in most eukaryotes and is essential for proper chromosome alignment and segregation during mitosis and meiosis. The NDC80 complex facilitates the attachment of kinetochores to spindle microtubules and contributes to the tension-sensing and checkpoint signaling that coordinates chromosome segregation.

Structure and function: Hec1 contains an N-terminal calponin-homology domain that binds microtubules, along with a coiled-coil region and an unstructured tail that modulates attachment stability. The tail is a substrate for Aurora B kinase, and its phosphorylation regulates the strength of kinetochore–microtubule attachments. Proper end-on attachments require dynamic regulation to ensure accurate chromosome bi-orientation and segregation.

Regulation and interactions: Hec1 operates within the KMN network and is recruited to kinetochores during early mitosis. Aurora B–mediated phosphorylation of Hec1’s tail weakens incorrect attachments, facilitating their release and realignment. Phosphatases counteract this process to stabilize correct attachments as tension is established.

Clinical significance: Aberrant expression of Hec1 is observed in several cancers and is associated with chromosomal instability and poor prognosis. Experimental depletion or pharmacological inhibition of Hec1 disrupts kinetochore–microtubule interactions, triggering mitotic arrest or cell death, making it a potential target for anti-mitotic cancer therapies.

Gene and nomenclature: In humans, Hec1 is encoded by the NDC80 gene. The alias HEC1 stands for Highly Expressed in Cancer 1 in some studies. The protein is widely conserved across eukaryotes.