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Evolutionarily conserved developmental pathways

Cell cycle 2: G1-S transition. Involvement of E2F, Cyclin D, Cyclin E and Retinoblastoma protein

Entrance into the DNA synthetic phase of the cell cycle, called the S phase is regulated by transcription factor E2F and both Cyclin D-Cyclin dependent kinase and Cyclin E-Cyclin dependent kinase heterodimers. In mammalian cells both Cyclin-Cdk heterodimers are held inactive by interactions with the p21 family of proteins, but in Drosophila there are no known p21 family members. In mammals the Cyclin E-cdk2 heterodimer is activated in a Myc dependent process. There are no known Drosophila Myc homologs.

E2F is a transcription factor held in an inactive heterodimer by the Retinoblastoma (Rb) protein. Phosphorylation of Rb by the Cyclin E-cdk heterodimer renders Rb incapable of binding E2F, allowing E2F to activate genes whose products are responsible for S phase functions, including Cyclin E. In mammalian systems there is an Rb-Cyclin D-Cdk interaction. No such interaction has been documented in Drosophila.

An E2F complex with an evolutionarily conserved accessory protein (DP) is necessary for E2F function as a transcriptional activator. In mammals there is an interaction of E2F and DP with p53, a regulator of cell proliferation. There is no known p53 homolog in Drosophila.

In mammalian cells there is an S phase interaction between E2F-1 and Cyclin A-cdk2. Cyclin A has no known S phase function in Drosophila. Cyclin E has cell cycle promoting functions other that phosphorylation of Rb (see Cell cycle 1: ORC and RLF).

Drosophila                    Homologs in other species ----------                    ----------------------------Cyclin D                      Vertebrates: Cyclin DCyclin E                      Vertebrates: Cyclin ECdc2c (See cyclin D)          Mammalian: Cyclin dependent kinase (Cdk2)dacapo                        Mammalian: p21 familyDmyc                          Mammalian: MycRBF (See E2F)                 Mammalian: Retinoblastoma family proteinsE2F                           Mammalian: E2F-1 to E2F-5DP (See E2F)                  Mammalian: DP-1?                             Mammalian: p53

date revised: 13 Oct 96

Developmental Pathways conserved in Evolution

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