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Evolutionarily conserved developmental pathways

Cell cycle 3: The G2-M transition - Cyclin A, Cyclin B, Cdc2, Wee kinase and Cdc25 phosphatase

Cyclin A plays a dual role in vertebrates, involved in both S phase and in the G2-M transition. In association with E2F it helps to terminate activation of the transcription of genes involved in DNA replication. Later in the cycle, depletion of Cyclin A arrests cells in G2. Thus Cyclin A is required for progression from G2 to M. In Drosophila, no S phase role has been detected for Cyclin A. In vertebrates Cyclin B is involved in a checkpoint that prevents the initiation of mitosis until S-phase is completed. No such function function has been documented in Drosophila.

Wee kinase regulates cdc2, the active kinase of the cyclin/cyclin dependent kinase dimer, by phosphorylation. The conserved Cdc25 phosphatase homolog, activates mitosis by removing phosphate groups from cdc2. Warts/Lats is a negative regulator of cdc2.

The cdc2/Cyclin B heterodimer was first characterized as maturation promoting factor, or MPF. MPF activity drives the events of early mitosis such as nuclear breakdown, chromosome condensation and spindle formation by phosphorylating cellular substrates. While cdc2 (the catalytic subunit of the MPF heterodimer) is required to drive the events of early mitosis, it must be inactivated by a ubiquitin based destruction mechanism to allow the events of late mitosis to proceed.

The metaphase-anaphase transition is a mitotic checkpoint. At this juncture the cell is able to monitor the integrity of its spindle before proceeding to inactivate MPF and initiate chromosome separation. The fact that Cyclin B/cdc2 is degraded at the metaphase-anaphase transition, suggests that MPF is the direct target of this checkpoint.

Drosophila                        Homologs in other species 
----------                        ----------------------------

String                            S. pombe: Cdc 25 
                                  Vertebrates: Cdc 25 homologs

Wee1 kinase (See Cdc2)            S. pombe: Wee kinase 
                                  Vertebrates: Wee kinase

Cyclin A                          Vertebrates: Cyclin A

Cyclin B                          Vertebrates: Cyclin B

cdc2                              Vertebrates: cdc2

warts                              Vertebrates: LATS1

date revised: 13 Oct 96

Developmental Pathways conserved in Evolution

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