Retinoblastoma protein family in cell cycle and cancer: A review

Abstract

Two genes, p107 and Rb2/p130, are strictly related to RB, the most investigated tumor suppressor gene, responsible for susceptibility to retinoblastoma. The products of these three genes, namely pRb, p107, and pRb2/p130 are characterized by a peculiar steric conformation, called "pocket," responsible for most of the functional interactions characterizing the activity of these proteins in the homeostasis of the cell cycle. The interest in these genes and proteins springs from their ability to regulate cell cycle processes negatively, being able, for example, to dramatically slow down neoplastic growth. So far, among these genes, only RB is firmly established to act as a tumor suppressor, because its lack-of-function is clearly involved in tumor onset and progression. It has been found deleted or mutated in most retinoblastomas and sarcomas, but its inactivation is likely to play a crucial role in other types of human cancers. The two other members of the family have been discovered more recently and are currently under extensive investigation. We review analogies and differences among the pocket protein family members, in an attempt to understand their functions in normal and cancer cells.

Molecular analysis of arterial stenosis in rat carotids

“…The Rb2/p130 gene is closely related to Rb, since it is a tumor suppressor gene and induces cellular differentiation (Paggi et al, 1996;Claudio et al, 1999), although it also shows important functional differences in comparison to other members of the Rb family. As shown in Figure 1, the Rb2 expression level shows a 5-fold decrease soon after arterial injury.…”

Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression

“…In late G1, the protein becomes phosphorlyated at restriction point and phosphorylation increases in S phases and at the G2M phase transition (Buchkovich et al 1989). This pRb is a nuclear phospho-protein and is regulated in a cell cycle-dependent manner by phosphorylation, and are critical targets for inactivation by transforming oncoproteins (Howard et al 2000;Paggi et al 1996Paggi et al , 2003. This protein bind to and modulate the activity of E2F family of transcription factors that induce the transcription of genes needed for the cell cycle progression through G1, S, G2 and M phases (Ewen 1994).…”

Mineral fibre toxicity: expression of retinoblastoma (Rb) and phospho-retinoblastoma (pRb) protein in alveolar epithelial and mesothelial cell lines exposed to fluoro-edenite fibres

“…The Rb family includes three members, phospho-retinoblastoma (pRb), p107 and pRb2/p130 (Paggi et al 1996), called "pocket proteins", that are phosphorylated in a cell cycle-dependent manner (Giordano et al 1991) and exert a pivotal role in the negative control of the cell cycle and in tumour progression (Giacinti and Giordano 2006).…”