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Target intelligence / Profile preview
Kinetochore-associated protein 1 (KNTC1)
- Target
- KNTC1
- Molecular classification
- Other (Kinetochore protein), Cell cycle regulatory protein, Mitotic checkpoint complex member
01
Overview
Kinetochore-associated protein 1 (KNTC1) is a key component of the outer kinetochore that is crucial for the correct segregation of chromosomes during mitosis. KNTC1 is part of the RZZ complex (with ZW10 and ZWILCH), which recruits dynein-dynactin and MAD1-MAD2 complexes to the kinetochore, activates the spindle assembly checkpoint, and delays anaphase onset if kinetochores are improperly attached to spindle microtubules[4][5]. KNTC1 is essential for cell cycle regulation and maintenance of genomic stability; abnormal expression is associated with various cancers and correlates with poor prognosis[1][2][4]. Knockdown of KNTC1 impairs cell division, promotes apoptosis, and reduces tumorigenicity[1][2]. Although not targeted by approved drugs, KNTC1 is a potential therapeutic target for cancer intervention strategies focusing on cell division and chromosomal stability[1][2].
- Other names
- KNTC1KIAA0166RODHsRODRodhRodRough deal homologcentromere/kinetochore protein
02
Mechanism of action
Drugs or genetic interventions (e.g., shRNA) that downregulate KNTC1 suppress cell proliferation, induce apoptosis, and reduce migration/invasion in cancer cells[1][2].
03
Biological functions
Chromosome segregation during mitosisSpindle assembly checkpoint activationRecruitment of dynein-dynactin/MAD1-MAD2 complexes to kinetochoresRegulation of cell cycleMaintenance of genomic stability
04
Disease associations
Cancer (including non-small-cell lung cancer, pancreatic cancer, cervical cancer, large intestine adenocarcinoma, and prostate squamous cell carcinoma)Other (Aneuploidy, chromosomal instability)
05
Safety considerations
Depletion or loss of KNTC1 results in abnormal chromosome segregation, aneuploidy, and chromosomal instability (CIN); targeting KNTC1 may thus cause adverse effects on cell viability and genetic integrity in normal tissues[4].
06
Biomarkers
High KNTC1 expression is a biomarker of poor prognosis in cancers (e.g., NSCLC and pancreatic cancer)
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