If cyclin-dependent kinase (CDK) is to a cell as an engine is to a car, then cyclins and CKI are:a. The key and ignition, respectively
The cell cycle is connected with signal transduction pathways as well as gene expression. Although the S and M phases rarely are subjected to changes imposed by extracellular signals, the G1 and G2 phases are the primary periods when cells decide whether or not to move on to the next phase. During the G1 phase, cells receive green- or red-light signals, S phase entry or G 1 arrest, respectively. Growing cells proliferate only when supplied with appropriate mitogenic growth factors. Cells become committed to entry of the cell cycle only toward the end of G1. Mitogenic signals stimulate the activity of early Gl cyclin-dependent kinases (CDKs) (eg, cyclin D/CDK4) that inhibit the activity of pRb protein and activate the transcription factor called E2F to induce the expression of batteries of genes essential for G1-S progression. Meanwhile, cells also receive antiproliferative signals such as those from tumor suppressors. These antiproliferative signals also act in the G1 phase to stop cells' progress into the S phase by inducing CKI production. For example, when DNA is damaged, cells will repair the damage before entering the S phase. Therefore, G1 contains one of the most important checkpoints for cell cycle progression. If the analogy is made that CDK is to a cell as an engine is to a car, then cyclins and CKI are the gas pedal and brakes, respectively. Accelerated proliferation or improper cell cycle progression with damaged DNA would be disastrous. Genetic gain-of-function mutations in oncogenes (that often promote expression or activity of the cyclin/CDK complex) or loss-of-function mutations in tumor suppressor (that stimulate production of CKI) are causal factors for malignant transformation.