Generally, it is cyclin-dependent kinases (Cdks) that regulate the progression of the cell cycle - dna replication, mitosis, and cytokinesis. As a cell progresses through the cell cycle, Cdk activity may increase or decrease. This causes cyclical changes in the phosphorylation of intracellular proteins that activate or regulate significant events of the cell cycle. For example, an increase in Cdk activity at the start of mitosis may lead to an increase in phosphorylation of proteins that regulate nuclear envelope breakdown or spindle assembly. The activity of Cdks are dependent on proteins known as Cyclins. When Cdks are bound to cyclins, Cdks become active. When not bound to cyclins, Cdks do not have any protein kinase activity.