45. Throughout the cycle there are internal regulators to ensure that the cycle progresses appropriately. Specifically,
proteins known as cyclins and enzymes known as cyclin dependent kinases (CDKs) regulate key events
throughout the cell cycle. CDKs are activated when they bind to their corresponding cyclin and can then
phosphorylate molecules in the cell signaling pathway and activate parts of the cell cycle. Cyclin levels fluctuate
throughout the cell cycle, while CDK levels remain constant. The diagram below illustrates CDK1 which
activates with Cyclin A in G2 and Cyclin B in Mitosis and CDK4 and CDK6, which activate with Cyclin D in Gl.
In normal cells, the activated CDKs are tightly regulated. As mentioned, cyclin levels fluctuate, and this
fluctuation is due to molecules that can break down cyclins at the appropriate stage of the cell cycle, thereby
de-activating the CDKs. Cancer cells have mutated cell cycle genes that can lead to uncontrollable growth and
cell division, meaning that many components of the CDK pathways are unregulated. Cancer researchers are
looking into the efficacy of using CKIS (CDK inhibitors) to treat many types of cancer. As can be seen in the
diagram below, p16 inhibits active CDK4/6, p27 inhibits active CDK1 in G2, and p21 inhibits active CDK1 in
Mitosis. Using this information and the diagram below identify how each inhibitor shown can be an effective way
of treating cancer by regulating the cell cycle at that specific stage/checkpoint. (5 pts)