The Retinoblastoma-Like Protein Family: Still in the Shadow of the RB Gene?

Extract

Exactly 10 years ago, the field of cancer biology received a quantum boost with the realization that viral proteins from three unrelated DNA tumor viruses had evolved the capacity to transform cells by binding to a set of cellular proteins that included the retinoblastoma (RB) tumor suppressor gene product (1–3). From a biochemical perspective, this observation allowed the development of a working model where RB can mediate growth inhibition or promote cellular differentiation by reversibly binding to an increasingly complex list of cellular proteins (4,5). From a clinical perspective, this observation has led to the identification of several promising targets for cancer treatment (6), but it has also raised the controversial question of what role ubiquitous DNA tumor viruses may play in human disease (7–9). Over the past several years, two other RB-like gene products, designated RBL1/p107 (called RBL1 here) and RBL2/pRB2/ p130 (called RBL2 here), have been isolated (10–13). Although the RBL1 and RBL2 genes are structurally related and have each conserved the ability to bind to a similar group of nuclear transcription factors, our understanding of how they interrelate with each other is still undefined (5,14,15). For example, while each member of the RB-like family can suppress cell growth in vitro (16–19), only the RB gene has convincingly met criteria for a tumor suppressor gene (20).