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

Target
CDK1-CCNB1
Molecular classification
Enzyme, Serine/threonine protein kinase, Cyclin-dependent kinase
01

Overview

The Cyclin-dependent kinase 1-Cyclin B1 complex, historically known as the Maturation-Promoting Factor (MPF), is a master regulator of the G2 to M phase transition in the eukaryotic cell cycle (Source: UniProt P06493, P14635). It consists of the catalytic subunit Cyclin-dependent kinase 1 (CDK1) and its regulatory partner, Cyclin B1. Activation of this complex triggers the entry into mitosis by phosphorylating a wide array of substrates involved in nuclear envelope breakdown, chromosome condensation, and spindle assembly (Source: PubMed PMC3437343). In many cancers, the complex is overexpressed or constitutively active, driving uncontrolled cell proliferation and genomic instability (Source: PubMed PMC6163524). Consequently, it has become a significant therapeutic target, with several small-molecule inhibitors developed to arrest the cell cycle in the G2/M phase and induce apoptosis in malignant cells (Source: PubMed PMC4189000). These inhibitors typically act through ATP-competitive mechanisms to block the kinase activity of the CDK1 subunit. Clinical development of these drugs often focuses on hematological and solid tumors where Cyclin B1 levels are elevated. However, achieving high selectivity for CDK1 over other cyclin-dependent kinases remains a challenge, often leading to side effects like myelosuppression. Monitoring biomarkers such as Cyclin B1 expression and CDK1 phosphorylation status is crucial for assessing treatment efficacy. Overall, the CDK1-Cyclin B1 complex remains a cornerstone of cell cycle research and a high-priority target in oncology.

Other names
Maturation-promoting factorMitosis-promoting factorMPFcdc2-Cyclin B1 complexCDK1-Cyclin B1 complexp34cdc2-Cyclin B1
02

Mechanism of action

ATP-competitive inhibition of the CDK1 catalytic subunit, preventing the phosphorylation of downstream substrates required for mitotic entry.

03

Biological functions

Cell cycleG2/M transitionMitosisProtein phosphorylation
04

Disease associations

CancerBreast cancerLung cancerColorectal cancerLeukemia
05

Safety considerations

MyelosuppressionNeutropeniaGastrointestinal toxicityOff-target CDK inhibition
06

Interacting drugs

Dinaciclib

5 more in the full profile.

07

Biomarkers

Cyclin B1 expressionCDK1 phosphorylation (Tyr15)Ki-67 indexPhospho-Histone H3

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