Target intelligence / Profile preview

NDC80 kinetochore complex component (NDC80)

Target
NDC80
Molecular classification
Other (Structural kinetochore complex protein), Kinetochore-associated protein
01

Overview

NDC80 kinetochore complex component (commonly referred to as NDC80 or HEC1 in humans) is a highly conserved structural protein that is an essential subunit of the NDC80 complex, a heterotetrameric core complex forming the principal connection between spindle microtubules and centromeres during mitosis[1][2][3]. The human NDC80 complex consists of NDC80 (HEC1), NUF2, SPC24, and SPC25; together, they form an elongated rod-like structure with calponin-homology domains on the NDC80/NUF2 end for microtubule attachment and RWD domains on the SPC24/SPC25 end interacting with inner kinetochore proteins[1][2]. The complex ensures proper chromosome alignment, biorientation, and segregation, thus maintaining genomic stability; its dynamic regulation, via conformational changes and phosphorylation, is critical to correct kinetochore-microtubule attachments and spindle checkpoint signaling[1][3]. NDC80 is highly expressed in many human cancers and is being investigated both as a prognostic biomarker and as a potential therapeutic target to induce mitotic catastrophe selectively in rapidly dividing tumor cells[1][3]. However, due to its ubiquitous role in cell division, therapeutic targeting poses significant toxicity risks.

Other names
HEC1KNTC2HsHec1TID3Kinetochore protein Hec1Kinetochore-associated protein 2Retinoblastoma-associated protein HECHighly expressed in cancer proteinNdc80p (yeast homolog)Kinetochore protein NDC80 homologSpc25-interacting protein
02

Mechanism of action

Inhibition of kinetochore-microtubule attachment (mechanism for experimental inhibitors/antibodies) Disruption of NDC80 complex function leads to mitotic arrest and apoptosis in rapidly dividing cells (mainly cancer cell models)

03

Biological functions

Chromosome segregationKinetochore-microtubule attachmentMitotic spindle checkpoint regulationMechanical tension bearing during mitosisCorrection of erroneous kinetochore-microtubule attachments
04

Disease associations

Cancer (Highly expressed in several cancers)Chromosomal instability disordersAneuploidy-related diseases
05

Safety considerations

Essential for normal cell division; on-target inhibition could cause toxicity in proliferative normal tissues (bone marrow, gut, hair follicles).Potential for chromosomal missegregation, aneuploidy, and general cytotoxicity[1][3].Limited tumor specificity, raising concerns for therapeutic window.
06

Interacting drugs

No FDA-approved drugs are currently recognized to directly target NDC80 for therapy, but it is under investigation as a potential anticancer target[1][3].

2 more in the full profile.

07

Biomarkers

Overexpression of NDC80/HEC1 as a prognostic biomarker for certain cancers (e.g., colorectal, liver, breast, ovarian)[1].High NDC80 expression levels associated with poor prognosis in multiple cancer types.

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