Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F

Abstract

The cellular protein p107 and the retinoblastoma protein (pRB) have many features in common. Most strikingly, they contain homologous protein domains that mediate interaction with the oncoproteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen. In cells that do not contain these viral oncoproteins, pRB interacts with the cellular transcription factor E2F or a related protein termed DRTF1. E2F associates with a form of pRB that is found primarily in G1 cells. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB. Here, we report that p107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that p107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and p107, E1A and large-T antigen target two distinct aspects of E2F regulation.

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

“…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). Indeed, in addition to the cell cycle, the RB family proteins regulate a wide spectrum of complex biological phenomena, as differentiation, embryonic development, apoptosis and senescence ( (Riley et al, 1994;Sidle et al, 1996;Herwig and Strauss, 1997;Stiegler et al, 1998;Thomas et al, 2003;Liu et al, 2004;Kapic et al, 2006) and references therein).…”

Cell cycle arrest and morphological alterations following microinjection of NIH3T3 cells with Puraα

“…However, at this time it is not known whether Pura binding to Rb serves any functional role in the cell cycle. In addition, it is not known whether Pura binds to other Rb-like proteins, such as p107 or p130, which may play a role in cell cycle events (Cao et al, 1992;Cobrinik et al, 1993;Ewen et al, 1991;Hannon et al, 1993;Li et al, 1993;Mayol et al, 1993). In human cells both p107 (Devoto et al, 1992) and p130 (Hannon et al, 1993) may be found in complexes with Cyclin A and CDK2, proteins now believed to associated with Pura (Itoh et al, 1998).…”

Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc

“…Among them are p107 and p130 (for review see Lam and LaThange, 1994;Sherr, 1995). More recently, it has been shown that p107 is phosphorylated by cyclin D/CDK4 and by cyclin E/ CDK2 complexes (Xiao et al, 1996;Lees et al, 1992) and that p107 is able to bind E2F (Starostik et al, 1996;Xiao et al, 1996;Zhu et al, 1995;Zamanian and LaThangue, 1993;Schwarz et al, 1993;Lees et al, 1992;Cao et al, 1992) but also the product of the c-Myc proto-oncogene (Beijersbergen et al, 1994Gu et al, 1994).…”