MPF, or Maturation-Promoting Factor, is the molecular switch that pushes cells into mitosis, the phase of the cell cycle where a cell physically divides. It’s a two-part protein complex made of cyclin B1 and CDK1 (a cyclin-dependent kinase), and its core job is to phosphorylate, or chemically tag, dozens of proteins inside the cell to trigger the dramatic structural changes that division requires: the nuclear envelope breaks apart, chromosomes condense into tight bundles, and the machinery that pulls chromosomes to opposite ends of the cell assembles.
The Two Parts of MPF
MPF is not a single protein. It’s a partnership between cyclin B1 and CDK1. CDK1 is the enzyme that does the actual work of tagging other proteins with phosphate groups, but it can’t function on its own. It needs cyclin B1 to bind to it and switch it on. Think of CDK1 as an engine and cyclin B1 as the ignition key.
Cyclin B1 levels rise steadily as the cell moves through the earlier phases of the cell cycle. It begins accumulating during S phase, when DNA is being copied, and continues building through G2 phase. But even though cyclin B1 is present and bound to CDK1, the complex stays inactive for most of this time. A pair of enzymes called Wee1 and Myt1 keep CDK1 locked in an “off” state by attaching inhibitory phosphate groups to it. The cell essentially builds up a stockpile of inactive MPF, waiting for the right moment to flip it on all at once.
How MPF Gets Activated
The transition from G2 into mitosis happens fast, and that speed comes from a clever positive feedback loop. When the cell is ready to divide, an enzyme called Cdc25 removes the inhibitory phosphate groups from CDK1, activating the MPF complex. Here’s where it gets interesting: once active, MPF phosphorylates Cdc25 itself, making Cdc25 work even faster. At the same time, MPF phosphorylates Wee1 and Myt1, the enzymes that were keeping it turned off, disabling them.
This creates a rapid, self-reinforcing chain reaction. More active MPF means more Cdc25 activation, which means even more active MPF. The result is a sharp, nearly irreversible flip from “not dividing” to “dividing.” Researchers describe this as a bistable switch, meaning the cell doesn’t gradually slide into mitosis. It snaps into it.
What MPF Does Once Active
With MPF fully switched on, it phosphorylates a wide range of target proteins throughout the cell, setting off the visible events of mitosis. Nuclear envelope breakdown is one of the most dramatic. MPF tags structural proteins called lamins that form a mesh lining the inside of the nuclear membrane. Once phosphorylated, the lamin mesh disassembles, and the nuclear envelope fragments.
MPF activity also drives chromosome condensation. During interphase, DNA exists as loose, spread-out chromatin. For chromosomes to be physically pulled apart without tangling or breaking, they need to be tightly compacted. MPF contributes to this condensation both directly, through phosphorylation of condensin complexes, and indirectly, by activating a kinase called Greatwall. Greatwall suppresses an opposing enzyme (a phosphatase called PP2A-B55) that would otherwise undo MPF’s work. Without this suppression, cells that enter mitosis display defective chromosome condensation, failed chromosome separation, and disordered division.
Beyond these two headline events, MPF also helps reorganize the cell’s internal skeleton to build the mitotic spindle, the structure that attaches to chromosomes and pulls them apart.
How the Cell Keeps Mitosis in Check
Cells have a safety mechanism called the spindle assembly checkpoint that monitors whether all chromosomes are properly attached to the spindle before allowing division to proceed. This checkpoint works by preventing the destruction of cyclin B, which keeps MPF active and holds the cell in mitosis until everything is correctly aligned. In yeast experiments, cells engineered to lack this checkpoint fail to stabilize cyclin B when spindles are disrupted, and they barrel through division with misaligned chromosomes.
How MPF Gets Shut Off
Exiting mitosis requires MPF to be completely inactivated. This happens through targeted destruction of cyclin B1. A large protein complex called the Anaphase-Promoting Complex (APC/C) attaches small molecular tags called ubiquitin to cyclin B, marking it for degradation by the cell’s protein-recycling machinery. Without its cyclin B partner, CDK1 goes inactive, and MPF activity disappears.
The APC/C works in stages. First, partnered with an activator called Cdc20, it triggers the separation of sister chromatids (the paired copies of each chromosome) and begins degrading cyclin B. This initial wave of cyclin destruction releases another enzyme that further tips the balance against CDK1. A second wave of APC/C activity, this time partnered with a different activator called Cdh1, finishes the job by destroying remaining cyclins and allowing the cell to fully reset.
Once both MPF and its S-phase counterpart are gone, the cell re-enters G1, the resting phase. DNA replication origins can be relicensed, and the whole cycle can begin again.
MPF Activity Through the Cell Cycle
MPF levels follow a predictable wave pattern across the cell cycle. Activity is essentially zero during G1, when the cell is growing and preparing to copy its DNA. It remains low through S phase, even as cyclin B begins to accumulate, because CDK1 is held inactive by Wee1 and Myt1. MPF activity peaks sharply at the G2/M transition and stays high throughout mitosis, then crashes back to zero as cyclin B is destroyed during mitotic exit.
This oscillation between high and low MPF activity is what gives the cell cycle its rhythmic, repeating character. The buildup of cyclin B followed by its abrupt destruction acts as a molecular clock that ensures each round of division happens in the correct order: DNA replication first, then chromosome separation.
How MPF Was Discovered
The name “Maturation-Promoting Factor” comes from experiments in frog eggs during the late 1960s and 1970s. Yoshio Masui found that injecting cytoplasm from a mature frog egg into an immature one could force the immature egg to undergo maturation, the final steps of meiosis that prepare an egg for fertilization. The unknown substance responsible was called Maturation-Promoting Factor. Years later, when the same activity was found to drive mitosis in all dividing cells, the “M” was sometimes reinterpreted as “Mitosis-Promoting Factor,” though both names refer to the same cyclin B-CDK1 complex.
MPF and Cancer
Because MPF is the final trigger for cell division, problems with its regulation can contribute to uncontrolled proliferation. Tumor cells generally cycle faster than normal cells and often show elevated levels of cyclins and their partner kinases. Overexpression of cyclin B or loss of the checkpoints that control MPF activation can allow cells to divide when they shouldn’t, accumulating DNA damage and chromosomal errors along the way. The cyclin B-CDK1 complex sits at a critical control point, and its dysregulation is one of many molecular changes that distinguish cancer cells from healthy ones.