Cyclin

Control of the cell cycle is regulated by a multitude of cellular events and processes. The cyclin dependent kinases (CDK) regulate many of these pathways and constitute an active complex when associated with their cyclin partners. This activity is controlled primarily by phosphorylation, which determines subcellular localization of the CDK/cyclin complex (1,2). Some phosphorylation events control the function of cytoplasmic retention sequences while other events regulate nuclear localization and export sequence function (3,4). Cyclin and cyclin-dependent kinase inhibitor (CKI) levels are regulated by ubiquitination and degradation via the ubiquitin proteasome pathway (5). A variety of CKI proteins associate with these complexes and modulate access to regulatory domains on cyclins (6). Additional complexity is generated as the controlled protein levels of each cyclin oscillate with the stages of cell cycle. Increased expression of Cyclin D1 is associated with certain types of cancer (7,8) and may associate with TSC2 (tuberin) independent of its Cdk partner (9).

The cell cycle can be divided into four phases, G1 (diploid): preparation for DNA replication and protein synthesis; S (diploid to tetraploid): DNA syn-thesis; G2 (tetraploid): preparation for mitosis; and M (tetraploid): mitosis. To ensure the stability and repeatability of the cell cycle, the whole process of cell cycle is driven by different cyclin-CDK complex, and precisely regulated by cell cycle checkpoint at the specifc point (thick arrow represents a different cell cycle phase, thin arrow indicates the expression of cyclin in different phases).