A Meiotic B-type Cyclin Selectively Drives Mitotic Progression and Fidelity in Cancer Cells
Year: 2026
Type: preprint
Abstract: Cell cycle transitions are driven by cyclins in complex with cyclin-dependent kinases (CDK). Here, we demonstrate that cyclin B3, an evolutionarily divergent B-type cyclin previously thought to function exclusively in female meiosis, is expressed in mitotic cells and interacts with both CDK1 and CDK2. We show that cyclin B3-CDK1/2 is essential for timely mitotic progression by ensuring proper chromosome alignment and stable kinetochore-microtubule interactions, while its overexpression accelerates mitosis and improves chromosome alignment kinetics. Through phospho-mass spectrometry, we identify several kinetochore and mitotic spindle components as substrates of cyclin B3-CDK1/2 in mitosis. Notably, cyclin B3 depletion disrupts mitotic progression in most cancer cell lines tested - including colorectal, osteosarcoma, and breast cancer models - while non-transformed cells are largely unaffected. These findings identify cyclin B3-CDK1/2 as a novel driver of mitotic progression and reveal a preferential dependency in a subset of cancer cells that may represent a potential therapeutic vulnerability.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, Cancer Research Coordinating Committee, National Institutes of Health, Office of the President, University of California, National Cancer Institute, National Institute of General Medical Sciences, Center for Complex Biological Systems, University of California, Irvine
Awards: Elucidating the role of cyclin B3 in cancer cell mitosis., Graduate Research Fellowship Program (GRFP), G4658115531, Systems Biology of Morphogeneisis and Spatial Information Flow, Developmental regulation of the cell cycle machinery, Cancer Center Support Grant, Advancing Proteomics Technologies to Decipher the Ubiquitin-Proteasome System
OpenAlex ID: W7214765917