Editing G2 phase (section)

=== Positive feedback ===
The positive feedback loop mentioned above, in which cyclin-B1/CDK1 promotes its own activation by inhibiting Wee1 and Myst1 and activating cdc25, does not inherently include a “trigger” mechanism to initiate the feedback loop. Recently, evidence has emerged suggesting a more important role for [[cyclin A2]]/CDK complexes in regulating the initiation of this switch. Cyclin A2/[[CDK2 (gene)|CDK2]] activity begins in early S phase and increases during G<sub>2</sub>. Cdc25B has been shown to dephosphorylate Tyr15 on CDK2 in early-to-mid G<sub>2</sub> in a manner similar to the aforementioned CDK1 mechanism. Downregulation of cyclin A2 in U2OS cells delays cyclin-B1/CDK1 activation by increasing Wee1 activity and lowering Plk1 and Cdc25C activity. However, cyclin A2/CDK complexes do not function strictly as activators of cyclin B1/CDK1 in G<sub>2</sub>, as CDK2 has been shown to be required for activation of the p53-independent G<sub>2</sub> checkpoint activity, perhaps through a stabilizing phosphorylation on [[Cdc6]]. CDK2-/- cells also have aberrantly high levels of Cdc25A. Cyclin A2/CDK1 has also been shown to mediate proteasomal destruction of Cdc25B. These pathways are often deregulated in cancer.<ref name=":0" />