Maturation-Promoting Factor (MPF) is a protein complex that regulates cell division. It functions as a chemical trigger, ensuring the cell transitions from preparation phases into nuclear and cellular division. MPF activity is tightly controlled, rising and falling cyclically to impose order on the cell’s replication process. It acts at a checkpoint, committing the cell to the final stages of division only after prior steps, such as DNA replication, have been successfully completed. By governing the entrance into mitosis, MPF ensures the integrity of the genome is maintained during cell proliferation.
The Cell Cycle Framework
The life of a proliferating cell is divided into the cell cycle, which consists of four main phases. Gap 1 (\(G_1\)) is a period of cell growth where the cell synthesizes new proteins and organelles. Following \(G_1\) is the Synthesis (\(S\)) phase, during which the cell’s entire genome is replicated, resulting in duplicate sets of chromosomes. The cell then enters Gap 2 (\(G_2\)), a second growth phase focused on synthesizing proteins and preparing structures for cell division.
These first three stages—\(G_1\), \(S\), and \(G_2\)—are collectively grouped as Interphase, representing the time between successive cell divisions. The final stage is the Mitotic (\(M\)) phase, which encompasses the division of the nucleus (mitosis) and the division of the cytoplasm (cytokinesis). MPF’s regulatory function is centered on the transition point between the \(G_2\) phase and the \(M\) phase, known as the \(G_2\)/\(M\) checkpoint. This checkpoint determines whether the cell is prepared to begin separating its duplicated chromosomes.
MPF Composition and Assembly
Maturation-Promoting Factor is formed by the association of two distinct protein subunits. One subunit is the Cyclin-Dependent Kinase (Cdk), which provides the enzymatic activity. For the \(G_2\)/\(M\) transition, this is primarily Cdk1, a kinase that uses ATP to add phosphate groups to target proteins. Cdk1 is present throughout the entire cell cycle but remains inactive on its own.
The second subunit is a regulatory protein called Cyclin, specifically Mitotic Cyclin (Cyclin B). Unlike Cdk1, the concentration of Cyclin B fluctuates, being synthesized in \(S\) and \(G_2\) phases and degraded during \(M\) phase. The MPF complex assembly occurs when Cyclin B binds to the inactive Cdk1 subunit, forming pre-MPF. This binding is necessary for the Cdk1 enzyme to acquire catalytic activity.
Activating MPF to Enter Mitosis
The formation of pre-MPF requires a precise sequence of phosphorylation and dephosphorylation events for full activation. While Cyclin B binds to Cdk1, an inhibitory kinase called Wee1 adds a phosphate group to Cdk1, locking the complex in an inactive state. Concurrently, an activating kinase phosphorylates Cdk1 at a separate site, which is necessary for eventual activity, but the inhibitory phosphates override this effect.
The switch to full activation is performed by the phosphatase enzyme Cdc25, which removes the inhibitory phosphate groups from the Cdk1 subunit. The Cdk1-Cyclin B complex promotes the activation of Cdc25, creating a positive feedback loop. This rapidly converts available pre-MPF into fully active MPF, generating a wave of kinase activity that initiates the structural changes of the \(M\) phase.
Once active, MPF phosphorylates a broad array of target proteins to drive the cell into mitosis. This includes the phosphorylation of lamins, which leads to the breakdown of the nuclear envelope. MPF also phosphorylates condensin proteins, triggering the coiling of DNA necessary for chromosome condensation. Furthermore, MPF kinase activity promotes the dynamic instability of microtubules, which is required for the assembly of the mitotic spindle apparatus.
The Role of Degradation in Cell Cycle Exit
The completion of mitosis requires the inactivation of MPF activity. This process is governed by the Anaphase Promoting Complex/Cyclosome (APC/C), which functions as an E3 ubiquitin ligase. The APC/C recognizes and targets cell cycle proteins for destruction by the proteasome, the cell’s primary protein-degrading machinery.
The APC/C targets the Mitotic Cyclin (Cyclin B) subunit of MPF for degradation. Once activated, the APC/C attaches ubiquitin onto Cyclin B, marking the protein for destruction. The ubiquitinated Cyclin B is then degraded by the 26S proteasome.
The destruction of the Cyclin B subunit causes the Cdk1 subunit to lose its catalytic activity, leading to MPF inactivation. This drop in kinase activity is necessary for the cell to proceed with the final events of mitosis, including the separation of sister chromatids during anaphase. MPF inactivation allows the dephosphorylation of its substrates, enabling the nuclear envelope to reform and chromosomes to decondense, allowing the cell to exit the \(M\) phase and proceed into \(G_1\).