AP Syllabus focus:
‘Interactions between cyclins and cyclin-dependent kinases drive cells through the cycle by activating or inactivating target proteins.’
Cyclins and cyclin-dependent kinases (CDKs) form a molecular control system that times major cell-cycle events. By switching key proteins on or off through phosphorylation, they coordinate orderly progression through cell division.
Core idea: a kinase “engine” plus a changing “key”
Cell-cycle control relies on protein complexes whose activity rises and falls. The central logic is that CDKs are broadly available, while cyclin availability changes, creating pulses of kinase activity that trigger cell-cycle steps.
Cyclin: A regulatory protein whose cellular concentration changes during the cell cycle; when present, it binds specific CDKs to help activate them.
A cyclin can be thought of as a timing signal: its synthesis and degradation control when a partnered CDK is active.
Cyclin-dependent kinase (CDK): A protein kinase that requires binding to a cyclin (and additional regulatory inputs) to phosphorylate target proteins and promote cell-cycle progression.
CDKs act by transferring phosphate groups to particular amino acids on target proteins, changing those proteins’ shape and function.
How cyclin–CDK complexes control progression
Building an active complex
Cyclin–CDK function depends on regulated assembly and activation.
Cyclin synthesis increases at specific points in the cycle (gene expression and translation raise cyclin concentration).
Cyclin binding to CDK changes CDK conformation, helping form an active catalytic site.
Regulatory phosphorylation further tunes activity:
This diagram summarizes the main control points that determine whether a cyclin–CDK complex is active. It shows how inhibitory phosphorylation (via Wee1/Myt1) and CKI binding keep CDKs off, while CAK phosphorylation and Cdc25-mediated dephosphorylation promote activation. It also includes ubiquitin-dependent proteolysis (SCF/APC) as the mechanism that removes inhibitors and destroys cyclins to terminate CDK activity. Source
Some phosphates are activating (stabilise an “on” conformation).
Others are inhibitory (block substrate access) until removed.
Once active, the complex phosphorylates a defined set of target proteins that carry out the next cell-cycle events.
Phosphorylation changes protein activity
Cyclin–CDK complexes drive the cycle by activating or inactivating target proteins, including proteins that directly execute cell-cycle tasks.
Activation by phosphorylation may:
turn on enzymes needed for biosynthesis
promote assembly of large cellular structures by altering binding interactions
enable proteins to enter the nucleus and act on DNA-associated processes
Inactivation by phosphorylation may:
shut off proteins that maintain the previous stage
prevent re-initiation of completed events by disabling “licensing” factors
block opposing pathways that would delay progression
The same chemical mechanism—phosphorylation—can therefore produce opposite outcomes depending on the target protein’s structure and role.
Timing and directionality: why the cycle moves forward
Oscillating cyclin levels create pulses of CDK activity
This figure plots the changing concentrations of major cyclins across the cell-cycle phases (G1, S, G2, M). The rise-and-fall pattern highlights how cyclin availability is periodic, producing timed windows in which specific cyclin–CDK complexes can form and drive checkpoint transitions. The sharp declines illustrate cyclin degradation as a reset mechanism between stages. Source
A key feature is that cyclin concentration is cyclical, while many CDKs remain present.
Rising cyclin levels create a threshold: below it, CDK activity is low; above it, CDK activity increases sharply.
High cyclin–CDK activity triggers the events of that stage, then is followed by cyclin removal so the cell can transition.
Turning the signal off: cyclin removal
Cyclin–CDK action must be temporary to avoid repeating steps.
Cyclins are often marked for rapid destruction after they have done their job.
Cyclin loss dismantles the active complex, causing CDK activity to drop.
The fall in CDK activity allows the next stage’s regulators to dominate, preventing the cell from becoming “stuck” in one phase.
Reinforcement through feedback
Cyclin–CDK systems commonly include feedback that sharpens transitions.
Positive feedback: active cyclin–CDK can indirectly increase its own activation (for example, by promoting activation of more complexes), producing a fast, switch-like rise.
Negative feedback: cyclin–CDK activity can help trigger processes that lead to cyclin disappearance, ensuring activity is self-limiting.
These feedback features help make cell-cycle transitions decisive rather than gradual.
What students should be able to explain
Why cyclins are the variable component and CDKs are the catalytic component.
How cyclin binding and regulatory phosphorylation control when a CDK can act.
How phosphorylation of targets can activate or inactivate proteins to coordinate sequential events.
How cyclin removal resets the system so progression is directional and appropriately timed.
FAQ
They are often tagged with ubiquitin, targeting them to the proteasome.
This creates an abrupt drop in cyclin–CDK activity, helping enforce directionality.
Different cyclins alter CDK substrate recognition by changing docking interactions.
Localisation (e.g., nuclear entry) also restricts which targets are accessible.
Yes—CDKs may require an activating phosphate and/or removal of an inhibitory phosphate.
Protein inhibitors can also block the active site despite cyclin binding.
They may assay phosphorylation of known substrates or use antibodies to detect phospho-sites.
Fluorescent reporters can indicate kinase activity dynamics in living cells.
Oscillation prevents re-triggering of the same stage and allows orderly hand-offs between regulators.
It also enables sharp transitions when cyclin synthesis and destruction are tightly controlled.
Practice Questions
Describe how cyclins and CDKs work together to regulate progression through the cell cycle. (2 marks)
Cyclin binds to a CDK to form an active complex (1)
The cyclin–CDK complex phosphorylates target proteins, activating or inhibiting them to move the cell to the next stage (1)
Explain how changes in cyclin concentration and CDK activity can produce one-way transitions between cell-cycle stages. Your answer should refer to phosphorylation of target proteins and switching CDK activity on and off. (5 marks)
Cyclin levels rise and fall during the cycle, whereas CDKs are more constant (1)
When cyclin concentration rises, cyclin binds CDK and increases/permits its kinase activity (1)
Active cyclin–CDK phosphorylates specific target proteins, activating/inhibiting them to trigger the next stage (1)
Cyclin is removed/degraded so the cyclin–CDK complex dissociates and CDK activity decreases (1)
Feedback (positive to sharpen activation and/or negative to promote shutdown) helps make transitions switch-like and effectively one-way (1)
