10.7:
Positive Regulator Molecules
A cells cycle is positively regulated promoting progress through the stages via the interaction of two classes of proteins found in the cytoplasm. Cyclins and cyclin dependent kinases, or CDK.
By default, CDKs are always present in a cell in an inactivated form. They must bind to a specific cyclin to be activated. When this complex forms the CDK can phosphorylate a target protein which alters it's function and initiates the cell to advance to the next phase. In most cases, when a cyclin is degraded, the CDK is inactivated, signaling the end of a particular phase. For instance, during G1, when one type of cyclin, named D, is synthesized and binds to a CDK, the cell transitions into S phase, as another cyclin, E, peaks and forms a complex with CDK to promote DNA replication.
E is then degraded by cytoplasmic enzymes and cyclin A concentrations increase throughout the S phase and remain high into G2 to promote entry into the M phase when in an active complex.
After A is degraded, concentrations of cyclin B peak in M phase and the complex will activate the different stages of mitosis. When B levels drop, the cell exits mitosis and divides. Thus, levels of the four different cyclins vary in predictable patterns and combine with consistent CDKs at specific points to achieve forward momentum.
10.7:
Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Internal regulatory checkpoints ensure that a cell’s size, energy reserves, and DNA quality and completeness are sufficient to advance through the cell cycle. At these checkpoints, positive and negative regulators promote or inhibit a cell’s continuation through the cell cycle.
Positive regulators include two protein groups that allow cells to pass through regulatory checkpoints: cyclins and cyclin-dependent kinases (CDKs). These proteins are present in eukaryotes, ranging from yeast to humans.
Cyclins can be categorized as G1, G1/S, S, or M cyclins based on the cell cycle phase or transition they are most involved in. Generally, levels of a given cyclin are low during most of the cell cycle but abruptly increase at the checkpoint they most contribute to (G1 cyclins are an exception, as they are required throughout the cell cycle). The cyclin is then degraded by enzymes in the cytoplasm and its levels decline. Meanwhile, cyclins needed for the next checkpoints accumulate.
To regulate the cell cycle, cyclins must be bound to a Cyclin-dependent kinase (CDK)—a type of enzyme that attaches a phosphate group to modify the activity of a target protein. The CDK is only active when bound to a cyclin. Depending on the cyclin they are bound to, CDKs are directed to different target proteins that are needed to advance to a particular cell cycle stage.
Compared to cyclins, CDKs remain at relatively constant levels throughout the cell cycle. However, their activity and the proteins they target change according to varying levels of cyclins across the cell cycle.
Suggested Reading
Bai, Jingwen, Yaochen Li, and Guojun Zhang. “Cell Cycle Regulation and Anticancer Drug Discovery.” Cancer Biology & Medicine 14, no. 4 (November 2017): 348–62. [Source]
Laphanuwat, Phatthamon, and Siwanon Jirawatnotai. “Immunomodulatory Roles of Cell Cycle Regulators.” Frontiers in Cell and Developmental Biology 7 (2019). [Source]