This review provides a comprehensive overview of how mitotic cells drive the repurposing of proteins to fulfill mitosis-specific functions. To ensure the successful completion of cell division, the cell strategically reallocates its “workforce” by assigning additional functions to available proteins. Protein repurposing occurs at multiple levels of cellular organization and involves diverse mechanisms. At the protein level, proteins may gain mitosis-specific functions through post-translational modifications. At the structural level, proteins that typically maintain cellular architecture in interphase are co-opted to participate in mitotic spindle formation, chromosome condensation, and kinetochore assembly. Furthermore, the dynamic reorganization of the nuclear envelope and other organelles relies on the temporary reassignment of enzymes, structural proteins, and motor proteins to facilitate these changes. These adaptive mechanisms underscore the remarkable versatility of the cellular proteome in responding to the stringent requirements of mitosis. By leveraging the existing proteome for dual or multiple specialized roles, cells optimize resource usage while maintaining the precision needed to preserve genomic integrity and ensure the survival of the next generation of cells.

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