synMuv verité—Myb comes into focus

Over the past 25 years, tremendous progress has been made in the identification of the genetic alterations that cause cancer. The discovery of oncogenes and tumor-suppressor genes relied largely on studies of animal retroviruses, consistent chromosomal aberrations in human cancers, transfection of human tumor DNA into rodent cells, DNA tumor viruses, and rare familial cancer syndromes (Bishop 1995). A major challenge has been to understand the function of the protein products of these genes in both normal and malignant cells. In many cases studies of developmental genetics in model organisms have provided key insights that have illuminated the pathways that go awry in human cancer. In particular, the awesome power of beast genetics in the nematode and fruit fly has benefited from the speed and relatively low cost of forward genetics, their much lower degree of gene (and genome) duplication relative to vertebrates, their relatively small genome size, the accumulated knowledge about the genetics and development of these organisms, and the strong and highly interactive communities of researchers devoted to their study. However, the discovery of genetic pathways alone is not sufficient to understand the intricate workings and assembly of the machinery within the cell. In addition, biochemistry and cell biology are required to reveal the possible functions of the pieces of this machinery. In the happy event that genetic and biochemical approaches converge on the same picture of the world, each gains confidence and insight from the other. This article focuses on recent results that display just such a convergence that bears directly on our understanding of the RB-E2F pathway that is mutated in most, if not all, human cancers (Gagrica et al. 2004; Korenjak et al. 2004; Lewis et al. 2004).

'S wonderful! 'S Muv-Vul-ous!

In the early 1990s a remarkable series of discoveries revealed the existence and function …