Control of cancer progression by retinoblastoma phosphorylation. The invention provides a method based on the finding that phosphorylation of RB protein in the N-terminal domain, namely at Serine 249 and Threonine 252 of human RB, leads to a conformational change that makes RB insensitive to CDK inactivation, promoting a cell cycle delay that reduces cell proliferation in cancer cells. The method identifies as candidates to anticancer drugs those compounds that give rise to modifications analogous to those provoked by RB phosphorylation in the N-terminal domain, mainly increased affinity of RB for E2F, decreased transcription of E2F and/or decreased expression of E2F-dependent genes, increased RB binding to E2F-dependent promoters or decreased cell proliferation. The method can be also carried out measuring the expression of an indicator gene operatively linked to an E2F-dependent promoter. Expression vectors of mutated retinoblastoma proteins mimicking phosphorylation at the N-terminal domain are also provided for therapeutic use.
