The retinoblastoma gene product regulates progression through the G1 phase of the cell cycle

Retinoblastoma family proteins as key targets of the small DNA virus oncoproteins

“…The RB family proteins share a considerable structural homology, primarily at the level of the 'pocket' domain, a complex structure subdivided in A-domain, spacer and B-domain. A-and B-domains are the most conserved among the three RB proteins and are involved in common functional characteristics (Paggi et al, 1996;Mulligan and Jacks, 1998), the most relevant one being the ability to control the cell cycle by negative modulation of the transition between the G1 and S phases (Goodrich et al, 1991;Zhu et al, 1993;Claudio et al, 1994;Starostik et al, 1996). To perform this task, these 'pocket proteins' utilize mechanisms mostly related to inactivation of transcription factors (Kouzarides, 1995), such as those of the E2F family (Cao et al, 1992;Helin et al, 1992Helin et al, , 1993Shirodkar et al, 1992;Beijersbergen et al, 1994;Hijmans et al, 1995;Sardet et al, 1995;Hurford et al, 1997), that promote the cell entrance into the S phase (Ewen, 1994;Weinberg, 1995;Paggi et al, 1996;Mulligan and Jacks, 1998).…”

Identification of a p130 domain mediating interactions with cyclin A/cdk 2 and cyclin E/cdk 2 complexes

“…These observations ®rst suggested that the RB-related proteins (pRB, p107 and p130) control key checkpoints in cellular growth control. Supporting this hypothesis are observations that pRb, p107 and p130 each can suppress growth when overexpressed in certain tumor-derived cell lines (Huang et al, 1990;Goodrich et al, 1991;Templeton and Weinberg, 1991;Hinds et al, 1992;Smith and Nevins, 1995;Zhu et al, 1993Zhu et al, , 1995aClaudio et al, 1994). Whether p107 and p130 can function as tumors suppressor genes is unknown.…”

“…The retinoblastoma protein (pRB) normally functions to restrict cell cycle progression through the G 1 stage of the cell cycle and appears to mediate one such checkpoint (Goodrich et al, 1991;Mittnacht and Weinberg, 1991;Hinds et al, 1992;Qin et al, 1992;Dowdy et al, 1993;Ewen et al, 1993). Loss or mutation of the retinoblastoma gene is a frequently occurring event in the formation of a variety of human tumors (reviewed in Goodrich and Lee, 1993).…”

Functional association of TGF-β receptor II with cyclin B

“…TGFb inhibition of cell proliferation is via the induction and activation of the tumor suppressor gene products, p15 and p27 ,that coordinately inhibit Cdk function (Toyoshima and Hunter, 1994;Blain et al, 1997;Reynisdottir and Massague, 1997). In Mv1Lu lung epithelial cells, TGFb could prevent retinoblastoma (Rb) protein phosphorylation during G1 phase, and hypophosporylated forms of Rb suppress progression into the S phase (Laiho et al, 1990;Goodrich et al, 1991). By contrast, TGFb stimulates growth in established cell lines of mesenchymal origin and, in C3H mouse ®broblasts paradoxically, it induces cell cycling via activation of cyclin E-Cdk2 kinase (Ravitz et al, 1995).…”