G1 cyclins and control of the cell division cycle in normal and transformed cells

The G1 cyclins are clearly important factors that control progression through the eukaryotic cell cycle. The expression and activity of these factors are regulated at many different levels and in response to a large number of signals. Such complicated, multilevel controls on expression and activation of cyclin/cdk complexes permit exquisite and necessary coordination of the stages of the cell cycle. Any of the large number of pathways involved in the regulation of cyclin activity also can be disrupted, leading to inappropriate expression and/or activity of complexes containing cyclins D1, D2, D3, and E. Characterization of these regulatory mechanisms and their synergistic effects on the G1 cyclins and cell cycle progression is a major area of investigation. While little evidence exists indicating that dysregulation of cyclin activity is an initiating event leading to malignant transformation, many studies indicate that disruption of the normal expression and/or activity of the G1 cyclins contributes to the transformed phenotype, potentially by overcoming negative proliferative signals in G1.