What is Cyclins and cyclin-dependent kinases? — Biology

Definition 10.1 University Biology — Year 3 · Chapter 10 — Cell Cycle Control and Programmed Cell Death

The cell cycle — G1, S (replication), G2, M (mitosis) — is driven by a family of protein kinases, the cyclin-dependent kinases (CDKs), whose catalytic subunits are present throughout the cycle but active only when bound to a cyclin, a regulatory subunit whose concentration rises and falls in a fixed order: cyclin D with Cdk4/6 in G1 in response to growth factors, cyclin E with Cdk2 at the G1/S transition, cyclin A with Cdk2 through S, cyclin B with Cdk1 at the entry into mitosis. Each cyclin–CDK phosphorylates the proteins of its phase — replication origins, lamins, condensins, the enzymes of spindle assembly — and each is switched off by the destruction of its cyclin: ubiquitin ligases (SCF in G1/S, the anaphase-promoting complex, APC/C, in mitosis) tag the cyclins for the proteasome. The activity of Cdk1 is further gated by an inhibitory phosphorylation put on by the kinase Wee1 and removed by the phosphatase Cdc25, and by small inhibitor proteins (p21, p27, p16) that bind the complexes. The cycle is thus an ordered sequence of kinase waves, each wave ending in the proteolysis of what produced it.

The cycle as a sequence of cyclin–CDK waves, each ended by the destruction of its cyclin, with the three checkpoints (red bars) at which the cell asks whether to proceed.

Left: the phase plane of the oscillator. The S-shaped curve is the fast steady state of Cdk1 for each level of cyclin; the red loop is the cycle — slow accumulation along the low branch, a jump at C_2, fast degradation along the high branch, a jump back at C_1. Right: the resulting time course, a sawtooth of cyclin and a square wave of kinase. — Left: the phase plane of the oscillator. The S-shaped curve is the fast steady state of Cdk1 for each level of cyclin; the red loop is the cycle — slow accumulation along the low branch, a jump at $C_{2}$ , fast degradation along the high branch, a jump back at $C_{1}$ . Right: the resulting time course, a sawtooth of cyclin and a square wave of kinase.

Examples

Example 10.3 (Why the frog egg is a clock)

A fertilised frog egg divides twelve times in six hours with no growth, no transcription and no checkpoints, at intervals of $30\,\mathrm{min}$ : it is the oscillator of the theorem running bare, and an extract of its cytoplasm in a test tube goes on cycling, cyclin rising and falling, with nothing to divide. Adding a non-degradable cyclin B locks the extract in mitosis, since $C$ can never fall below $C_{1}$ ; blocking cyclin synthesis locks it in interphase. In a somatic cell the same engine is wrapped in the controls of the next section, which hold it at the thresholds until conditions are met, so that the period becomes a day rather than half an hour and can be indefinitely long.

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