MPF stands for maturation-promoting factor (also called M-phase-promoting factor), and it is the master switch that triggers cell division. It’s a protein complex made of two parts: a kinase called Cdk1 (the engine) and cyclin B (the ignition key). When these two proteins come together and the complex is activated, the cell commits to dividing. Without MPF, cells stall before mitosis and never enter the division phase.
How MPF Was Discovered
MPF was first identified in frog oocytes in the early 1970s by Yoshio Masui. The key experiment was elegantly simple: researchers took cytoplasm from a mature, dividing egg cell and injected it into an immature egg cell that was sitting in a resting state. The immature cell immediately began maturing and dividing. Something in that cytoplasm, a transferable activity, was pushing cells into division. Masui named it maturation-promoting factor. Later work in starfish oocytes confirmed the same activity existed across species, and decades of biochemistry eventually pinpointed the responsible molecules as the Cdk1-cyclin B complex.
The Two Subunits of MPF
MPF consists of two proteins that must join together to function. Cdk1 (cyclin-dependent kinase 1) is the catalytic subunit, meaning it’s the part that actually does the chemical work. On its own, though, Cdk1 is inactive. It needs its partner, cyclin B, which serves as the regulatory subunit. Cyclin B accumulates gradually throughout the cell cycle, and once enough of it binds to Cdk1, the complex can be switched on.
Even after Cdk1 and cyclin B pair up, the complex starts in an inactive state. Two specific sites on Cdk1 (called Threonine 14 and Tyrosine 15) are tagged with phosphate groups by an enzyme called Wee1, which keeps the complex locked in “off” mode. The cell only flips MPF to “on” when another enzyme, Cdc25, strips those phosphate groups away. This two-layer control system, building the complex and then separately activating it, ensures the cell doesn’t accidentally enter division too early.
How MPF Activates Itself
One of the most important features of MPF is that it creates a positive feedback loop. Once a small amount of active Cdk1-cyclin B appears, it does two things simultaneously: it activates more Cdc25 (the enzyme that turns on MPF) and it inactivates Wee1 (the enzyme that keeps MPF off). This means a tiny initial activation rapidly snowballs into full, irreversible commitment to cell division. The cell goes from “maybe dividing” to “definitely dividing” in minutes.
Recent research has expanded the classical definition of MPF beyond just Cdk1 and cyclin B. A second kinase called Greatwall also plays a critical role. Greatwall shuts down a phosphatase (a cleanup enzyme) that would otherwise undo the work of Cdk1. In experiments where cytoplasm is transferred between cells, both Cdk1-cyclin B and Greatwall are needed to push the recipient cell into division. So in the strictest sense, MPF is a system of at least two cooperating kinases rather than a single protein complex.
What MPF Does to the Cell
MPF is a kinase, which means it works by attaching phosphate groups to other proteins, changing their shape and behavior. The targets it modifies are precisely the ones needed to physically reorganize the cell for division.
Nuclear Envelope Breakdown
The nucleus is enclosed by a mesh of structural proteins called lamins that give it shape and rigidity. When MPF activates, it phosphorylates these lamins at specific sites. For example, it tags lamin A/C at three positions and lamin B1 at two. This phosphorylation causes the lamin mesh to fall apart, dissolving the nuclear envelope so that the chromosomes inside become accessible to the division machinery. Phosphorylation at just the key mitotic sites is enough to trigger lamin disassembly both in lab conditions and in living cells.
Chromosome Condensation
Before a cell can split its genetic material evenly, it needs to pack its long, loose DNA into compact chromosomes. MPF accomplishes this by phosphorylating components of a protein complex called condensin II. Specifically, Cdk1 tags one subunit of condensin II, which then allows another enzyme (Polo-like kinase 1) to bind and add further phosphate groups. This chain of events is required for chromosomes to condense on schedule during the early stages of mitosis. Cells carrying mutant versions of condensin II that can’t be phosphorylated by Cdk1 show delayed and disorganized chromosome compaction.
Spindle Assembly
MPF also promotes the reorganization of the cell’s internal skeleton into a mitotic spindle, the structure that pulls chromosomes apart. By phosphorylating proteins involved in microtubule dynamics, MPF helps convert the cell’s normal structural framework into the bipolar apparatus needed for chromosome separation.
How MPF Is Shut Off
Getting into mitosis is only half the job. The cell also needs to exit division cleanly, and that requires destroying MPF activity at just the right moment. This happens through targeted destruction of cyclin B.
Once all chromosomes are properly attached to the mitotic spindle, a surveillance system called the spindle assembly checkpoint turns off. This unleashes a large protein machine called the anaphase-promoting complex (APC/C), which tags cyclin B with a small protein marker called ubiquitin. Ubiquitin-tagged cyclin B is then rapidly chewed up by the cell’s protein recycling machinery. Without its cyclin B partner, Cdk1 goes inactive, MPF activity drops to zero, and the cell proceeds to split its chromosomes apart and divide into two daughter cells.
The speed of this process matters. Recent work has shown that chromosomes themselves help bring cyclin B close to the APC/C, ensuring that degradation happens rapidly once the checkpoint is satisfied. This spatial control prevents lingering MPF activity that could disrupt chromosome separation and cause genetic instability.
MPF Across Species
One of the remarkable features of MPF is how deeply conserved it is across the tree of life. The same basic Cdk1-cyclin B partnership drives cell division in yeast, frogs, starfish, flies, and humans. In budding yeast, Cdk1 goes by the name Cdc28. In fission yeast, it’s called Cdc2. In humans, it’s Cdk1. Despite the different names, these proteins are so similar that early experiments showed a human version could substitute for the yeast protein and still drive division. This conservation means that discoveries about MPF in simple organisms like yeast have directly informed our understanding of how human cells divide, and how that process goes wrong in cancer.
MPF and the G2/M Transition
The specific moment MPF controls is the transition from G2 phase (the gap after DNA replication) into M phase (mitosis). During G2, the cell has already copied all its DNA and is essentially waiting for the green light to divide. MPF activation is that green light. Cdk1 sits in its inactive, phosphorylated form throughout G1, S phase, and G2, held in check by Wee1. Only when the cell is ready, with DNA replication complete and no damage detected, does Cdc25 activate and tip the balance toward MPF activation.
This checkpoint function is why MPF matters beyond basic biology. Many cancer therapies target components of this pathway, because cancer cells often have defective controls over the G2/M transition. Understanding how MPF is regulated has provided a framework for identifying where cell division control breaks down in disease.