The retinoblastoma family: twins or distant cousins?

Abstract

The destiny of a cell--whether it undergoes division, differentiation or death--results from an intricate balance of many regulators, including oncoproteins, tumor-suppressor proteins and cell-cycle-associated proteins. One of the better-studied tumor suppressors is the retinoblastoma protein, known as pRb or p105. Two recently identified proteins, pRb2/p130 and p107, show structural and functional similarities to pRb, and these proteins and their orthologs make up the retinoblastoma (Rb) family. Members of the family have been found in animals and plants, and a related protein is known in the alga Chlamydomonas. Members of the Rb family are bound and inactivated by viral proteins and, in turn, bind cellular transcription factors and repress their function, and can also form complexes with cyclins and cyclin-dependent kinases and with histone deacetylases. They are found in the nucleus and their subnuclear localization depends on binding to the nuclear matrix. Members of the family form part of a signal-transduction pathway called the Rb pathway, which is important in cell-cycle regulation and have roles in growth suppression, differentiation and apoptosis in different organisms and cell types.

Figure 1

Comparison of the genomic structure of human retinoblastoma genes and of the functional domains in different Rb-related proteins. Boxes indicate exons of the human RB gene; hatched boxes indicate exons encoding domains A and B. Adapted from [7].

Figure 2

Phylogenetic tree illustrating the diversity of pRb in eight representatives of different phyla and kingdoms. Numbers are branch lengths, which correspond to the estimated evolutionary distance between protein sequences. The tree was constructed using ClustalW.