InterPro domain: IPR028309

This entry represents the retinoblastoma protein family, including retinoblastoma-associated protein (RB, also known as pRb, RB, p1051), retinoblastoma-like protein 1 (RBL1, also known as p107) and retinoblastoma-like protein 2 (RBL2, also known as RB2 or p130). Members of this family contain a conserved domain named the 'pocket' that interacts with the LXCXE motif found in viral proteins, such as SV40 large T antigen [ 1 ]. Therefore, this family is also called the pocket protein family.

In humans, RB is a tumour suppressor linked to several major cancers [ 2 ]. RB forms complexes with E2Fs and represses gene expression by recruiting chromatin remodeling factors, such as histone deacetylases (HDACs) to E2F-responsive promoters [ 3 , 4 ]. This interaction regulates genes necessary for DNA replication and cell cycle. Phosphorylation of RB family by CDK and cyclin complexes leads to release of the repressor complex and enables E2F-dependent gene expression [ 5 ]. Apart from E2Fs, RB also interacts with other transcription factors that govern cell differentiation [ 5 , 6 ].

RBL1 and RBL2 are the components of the DREAM complex, which represses cell cycle-dependent genes in quiescent cells and plays a role in the cell cycle-dependent activation of G2/M genes [ 7 , 8 ].

1. Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts? Cell Div 2, 26
2. Retinoblastoma: clues to human oncogenesis. Science 223, 1028-33
3. The RB and p53 pathways in cancer. Cancer Cell 2, 103-12
4. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14, 2393-409
5. The retinoblastoma gene family in differentiation and development. Oncogene 18, 7873-82
6. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol. Cell 8, 303-16
7. Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence. Mol. Cell 26, 539-51
8. LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes. Cell Cycle 6, 1903-13