The Cell Cycle

Nonproliferating cells are in the "no growth" (G₀) stage of the cell cycle. G₀ cells are expressing only those genes that are needed to maintain life and carry out any specialized function they normally have. To begin the first growth stage (G₁) of the cell cycle, cells must be signaled, usually by more than one growth factor. The binding of growth factors to their receptors may stimulate the receptor's tyrosine kinase activities, resulting in autophosphorylation and in the phosphorylation of other kinases. Most of these secondary kinases are serine-threonine kinases. In some cases, activated receptors stimulate G proteins that subsequently stimulate enzymes that produce second messengers. The second messengers often stimulate serine-threonine kinases. The serine-threonine kinases phosphorylate transcriptional activators or repressors, stimulating and inhibiting them, respectively. This results in the expression of a number of genes, in particular, the genes for G₁ phase cyclins: CDPKs, RNA polymerase, DNA helicase, and DNA polymerase. The accumulation of these proteins during G₁ is essential for DNA replication in the S phase of mitosis.

G₁ phase cyclins are regulatory subunits for proteins called mitosispromoting factors (MPFs). The catalytic subunits are designated Cdc (for cell division control), but are also known as Cdks (for cyclin-dependent kinases). The cyclin-Cdk complex is activated by phosphorylation and dephosphorylation of Cdk on certain threonines and tyrosines, which ultimately leads to DNA replication.

The second growth phase (G₂) occurs after DNA synthesis. G₂ cyclins begin to accumulate, increasing the activity of a new group of cell division control kinases that are activated by a sequence of phosphorylations and dephosphorylations. These kinases phosphorylate proteins called lamins in the nuclear membrane, scaffold proteins in the nucleus, and a microtubule associated protein kinase.

Phosphorylation of a chromosomal scaffold protein (believed to be a topoisomerase) results in the condensation of the solenoid chromosome structure onto a scaffold. Phosphorylation of lamins cause chromosomal detachment from the inner nuclear membrane and fragmentation of the nuclear membrane. Other phosphorylation events lead to tubulin polymerization necessary for mitotic divsion to ensue.