INTRODUCTION During development and tissue homeostasis, proliferating stem and progenitor cells ultimately give rise to daughter cells that acquire specialized functions. The terminal differentiation of such cells coincides with a permanent withdrawal from the cell division cycle. This cell cycle arrest is achieved by a combination of cell cycle regulators that include the retinoblastoma tumor suppressor (Rb) protein family of transcriptional corepressors, cyclin-dependent kinase (CDK)inhibitory proteins (CKIs) that bind and block CDKs, and E3 ubiquitin ligases such as the anaphase-promoting complex in association with the coactivator Cdh1/FZR1 (APC/C-FZR1) that promote protein degradation (1)