The well-known tumour suppressor functions of Retinoblastoma (RB) protein are mainly attributed to its cell-cycle blocking activities. But now on , Schertel and Conradt report that RB and its associated proteins also function by promoting apoptosis in differing ways. Their studies of lin-35 RB loss-of-function C. elegans mutants, in which the constitutive germ cell apoptosis that normally occurs in adult hermaphrodites is decreased, show that lin-35 promotes germ cell apoptosis by repressing ced-9- an anti-apoptotic gene and BCL2 orthologue. The genes dpl-1 DP, efl-1 E2F and efl-2 E2F, which encode proteins that complex with RB, also promote germ cell apoptosis, but they do so by inducing the expression of the pro-apoptotic genes ced-4 and ced-3. Finally, the authors show that lin-35, dpl-1 DP and efl-2 E2F also promote DNA-damage-induced apoptosis but by controlling the expression of different target genes and not via ced-9,ced-4 and ced-3. Together, these important findings provide new avenues of research for investigating the differing tumour-suppressor functions of RB, particularly in mammals.
