Cyclin-dependent kinase 1-Cyclin B1 complex (CDK1-CCNB1)

The Cyclin-dependent kinase 1-Cyclin B1 complex, historically known as the maturation-promoting factor (MPF), is the master regulator of the G2 to M phase transition in the eukaryotic cell cycle (UniProt P06493). CDK1 serves as the catalytic serine/threonine kinase, while Cyclin B1 acts as the essential regulatory subunit that controls the timing and localization of the complex's activity (UniProt P14635). During late G2, the complex is activated by CDC25 phosphatases, triggering mitosis by phosphorylating a wide array of substrates involved in nuclear envelope breakdown, chromosome condensation, and spindle assembly (Santamaria et al., 2007). In many cancers, this machinery is overexpressed or dysregulated to sustain rapid and uncontrolled cell division, making it a significant target for oncology drug development (Malumbres & Barbacid, 2009). Therapeutic strategies primarily involve small-molecule inhibitors, such as Dinaciclib and Alvocidib, which target the ATP-binding pocket of CDK1 to induce mitotic arrest and subsequent apoptosis in tumor cells. However, because CDK1 is essential for the division of all proliferating cells, these inhibitors often face challenges related to systemic toxicity and a narrow therapeutic index.

Other names

Maturation-promoting factorM-phase promoting factorMPFCDK1-Cyclin B1 complexG2/M transition machinery

Inhibition of the catalytic activity of CDK1 within the Cyclin B1 complex, preventing the phosphorylation of mitotic substrates and inducing G2/M phase arrest and apoptosis (Malumbres & Barbacid, 2009; UniProt P06493).