The overall cell production and cell content of an organ is determined by the rates of immigration, division, differentiation, emigration and death of cells. Abnormalities in any one of these processes can cause tissue atrophy or hypertrophy, which can lead to cancer [1, 2], autoimmunity [3, 4] or degenerative disorders [5]. Proliferation, differentiation and cell death must therefore be properly balanced. This is achieved, at least in part, through mechanisms that interconnect the signalling pathways regulating these processes. Although mutations affecting either cell division, cell death or cell differentiation, alone, can predispose to malignancy, abnormalities within two of these processes often act synergistically in cell transformation [6]. For example, increased cell cycling because of c-myc oncogene overexpression and reduced apoptosis expression because of bcl-2 oncogene deregulation cooperate in lymphomagenesis [1] and tumourigenesis in mammary glands [7].

Progression through the cell cycle is driven by the action of cyclin dependent kinases (CDKs)(reviewed in [8]). To function, CDKs must associate with cyclins, which are synthesized at specific stages of the cell cycle in response to mitogenic stimuli and certain cytokines [9]. Two major checkpoints control cell cycle progression; one at the G1/S boundary, when cells commit to DNA replication, and the other at the G2/M boundary when cells commit to mitotic division. A major function of cyclin–CDK complexes during transition through G1 and at the G1/S boundary is to overcome the block imposed by the retinoblastoma protein (Rb) and some of its relatives [8]. Hypophosphorylated Rb sequesters a number of transcriptional regulators, including members of the E2F/DP family [10], and therefore blocks their activities. When Rb is phosphorylated by cyclin–CDK complexes it releases the sequestered