ZW10 Interacting Kinetochore Protein (ZWINT) is a crucial component of the mitotic spindle checkpoint, playing a significant role in chromosome segregation during cell division. This protein is essential for the proper attachment of chromosomes to the spindle microtubules, ensuring accurate chromosome alignment and segregation. ZWINT has garnered attention due to its involvement in various cellular processes and its potential implications in cancer biology.
ZWINT was initially identified as a protein that interacts with Zeste White 10 (ZW10), a key player in the mitotic checkpoint. The protein is characterized by its ability to bind to kinetochores, which are protein structures on chromosomes that attach to spindle fibers during cell division. ZWINT is composed of several domains that facilitate its interaction with other kinetochore proteins and microtubules, making it an integral part of the kinetochore complex .
ZWINT functions as a scaffold protein, providing a platform for the assembly of other kinetochore proteins. It plays a pivotal role in the recruitment of the RZZ (Rod-ZW10-Zwilch) complex to the kinetochores, which is essential for the activation of the spindle assembly checkpoint (SAC). The SAC ensures that chromosomes are correctly attached to the spindle microtubules before the cell proceeds to anaphase, thereby preventing chromosome missegregation and aneuploidy .
Recent studies have highlighted the upregulation of ZWINT in various types of human cancers, including breast cancer. Elevated levels of ZWINT have been associated with poor prognosis and aggressive tumor characteristics. For instance, high ZWINT expression has been linked to positive human epidermal growth factor receptor 2 (HER2) expression, triple-negative breast cancer, younger age, basal-like subtype, and higher Scarff-Bloom-Richardson grades . These findings suggest that ZWINT may serve as a potential prognostic biomarker and therapeutic target in cancer treatment.
The recombinant form of ZWINT, produced through genetic engineering techniques, has been instrumental in studying its function and interactions. Human recombinant ZWINT is used in various research applications, including the investigation of its role in mitotic checkpoint signaling, chromosome segregation, and cancer progression. Additionally, recombinant ZWINT is utilized in drug discovery and development, aiming to identify compounds that can modulate its activity for therapeutic purposes.