Spc25

Spc25 is a protein component of the Ndc80 complex, a core part of the outer kinetochore that mediates the attachment of spindle microtubules to chromosomes during mitosis. In budding yeast, the protein is commonly referred to as Spc25p and is encoded by the SPC25 gene; in other eukaryotes, including humans, SPC25 denotes the ortholog of this kinetochore subunit. The Ndc80 complex is a four-protein assembly that includes Ndc80, Nuf2, Spc24, and Spc25, forming an elongated scaffold that couples centromeric chromatin to microtubules.

Spc25 forms a heterodimer with Spc24, and this Spc24–Spc25 unit associates with the Ndc80–Nuf2 pair to assemble the functional complex. The Spc24–Spc25 region contributes to the stability and architecture of the complex, helping to establish and maintain the microtubule-binding interface essential for robust kinetochore-microtubule interactions.

Localization and function: Spc25 localizes to kinetochores during mitosis and is essential for establishing stable kinetochore-microtubule attachments. Disruption of Spc25 or perturbation of the Ndc80 complex often results in defective chromosome congression, mis-segregation, and aneuploidy.

Regulation and conservation: The Ndc80 complex, including Spc25, is regulated by cell-cycle–dependent phosphorylation, with Aurora B kinase playing a key role in modulating attachment stability. Spc25 is highly conserved across eukaryotes, reflecting its fundamental role in chromosome segregation.

Clinical relevance: Given its central role in accurate mitosis, alterations in Spc25 or the Ndc80 complex can contribute to chromosomal instability observed in cancers. The complex is sometimes explored as a potential target for therapies aimed at disrupting mitosis in rapidly dividing cells.