Tumour suppressors--a fly's perspective

For a century, the little fruitfly Drosophila melanogaster has taught generations of geneticists about how genes control the development of a multicellular organism. More recently, Drosophila has begun to contribute more directly towards our understanding of human disease [Bernards A, Hariharan IK. Of flies and men-studying human disease in Drosophila. Curr Opin Genet Dev 2001, 11, 274-278]. It is capable of doing this because it shares many disease-related genes with us. For example, the Drosophila genome sequencing project has revealed that two thirds of the genes implicated in human cancers have a counterpart in the fly genome [Adams MD, Celniker SE, Holt RA, et al. The genome sequence of Drosophila melanogaster. Science 2000, 287, 2185-2195, Fortini ME, Skupski MP, Boguski MS, Hariharan IK. A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol 2000, 150, F23-30]. In particular, the fly has homologues of the Retinoblastoma protein (pRb) and of p53, two prototypical tumour suppressors which are inactivated in the majority of human tumours. Here, we will compare the fly's tumour suppressors with their human counterparts and we will review recent advances in our understanding of how these factors function in the fly.