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NUF2 (Kinetochore protein Nuf2) is a core component of the heterotetrameric NDC80 kinetochore complex, which is essential for stable microtubule attachment and accurate chromosome segregation during mitosis [2, 6]. It forms a dimer with NDC80 (also known as Hec1) and localizes to the outer plate of the kinetochore, where it mediates the connection between the centromere and spindle microtubules [1, 15]. Beyond its classical role in the cell cycle, recent evidence indicates that NUF2 is involved in ribosome biogenesis by regulating pre-rRNA transcription in the nucleolus [1, 3]. NUF2 is frequently overexpressed in a wide range of malignancies, including lung, breast, gastric, and colorectal cancers, where it promotes tumor cell proliferation, migration, and survival [4, 7, 21]. Due to its high expression in tumors and critical role in mitosis, NUF2 is considered a promising therapeutic target and a prognostic biomarker [7, 17, 29]. Experimental strategies to target NUF2 include small molecule inhibitors like quercetin, peptide vaccines, and CAR T-cell therapies, which aim to induce mitotic arrest and apoptosis in cancer cells [17, 18, 26]. Mutations in the NUF2 gene have also been linked to developmental disorders such as microcephaly and short stature [13, 14].
Inhibition of kinetochore-microtubule attachment, disruption of the NDC80 complex, induction of G2/M phase arrest and apoptosis, and inhibition of pre-rRNA transcription.
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