The Interactive Fly
Evolutionarily conserved developmental pathways
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 D Cyclin E Vertebrates: Cyclin E Cdc2c (See cyclin D) Mammalian: Cyclin dependent kinase (Cdk2) dacapo Mammalian: p21 family Dmyc Mammalian: Myc RBF (See E2F) Mammalian: Retinoblastoma family proteins E2F Mammalian: E2F-1 to E2F-5 DP (See E2F) Mammalian: DP-1 ? Mammalian: p53
date revised: 13 Oct 96
Developmental Pathways conserved in Evolution
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