Interaction Between Human Cyclin A and Adenovirus E1A-Associated p107 Protein

Abstract

The products of the adenovirus early region 1A (E1A) gene are potent oncoproteins when tested in standard transformation and immortalization assays. Many of the changes induced by E1A may be due to its interaction with cellular proteins. Four of these cellular proteins are the retinoblastoma protein (pRB), p107, cyclin A, and p33cdk2. The pRB and p107 proteins are structurally related and have several characteristics in common, including that they both bind to the SV40 large T oncoprotein as well as to E1A. Cyclin A and p33cdk2 are thought to function in the control of the cell cycle. They bind to one another, forming a kinase that closely resembles the cell cycle-regulating complexes containing p34cdc2. Cyclin A is now shown to bind to p107 in the absence of E1A. The association of p107 with cyclin A suggests a direct link between cell cycle control and the function of p107.

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

“…Studies on some of the above mentioned proteins have indicated that the residues homologous to the p130 cyclin binding region are directly involved in cyclin/cdk interactions. p107 has been shown to interact with both cyclins A and E and several studies have suggested that the region homologous to the p130 cyclin binding region is critical for these interactions Faha et al, 1992;Zhu et al, 1995a, b). A region similar to the p130 cyclin binding region is found at the amino-termini of p21 cip1 , p27 kip1 and p57 kip2 .…”

“…In addition to the interactions with the D cyclins, p107 and p130 stably interact with cyclin A/cdk2 and cyclin E/cdk2 complexes in vivo and in vitro Faha et al, 1992Faha et al, , 1993Lees et al, 1992;Hannon et al, 1993;Li et al, 1993;Peeper et al, 1993). This property is not held in common with pRB and the signi®cance of this di erence remains unclear.…”

“…For p107, the structural basis for the interactions with cyclins A and E has been examined and it has been determined that in vitro interactions between cyclin A and p107 are mediated by a part of p107 referred to as the spacer region Faha et al, 1992). In this report, we examine the basis for the interactions between p130 and cyclin A and cyclin E complexes and identify a region of p130 required for binding to cyclin A/cdk2 and cyclin E/cdk2 complexes in vitro and in vivo.…”

Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes.

“…Human cyclin A was initially identified as the p60 protein associated with the adenovirus ElA oncoprotein (Harlow et al, 1986;Giordano et al, 1989;Pines and Hunter, 1990). The association between cyclin A and ElA was later shown to be mediated by pRblO7, a homologue of the retinoblastoma susceptibility gene product pRblO5 (Ewen et al, 1991Faha et al, 1992). The cyclin A/pRblO7 complex was also found to contain CDK2 and E2F (Mudryj et al, 1991;Cao et al, 1992;Devoto et al, 1992;Pagano et al, 1992a;Shirodkar et al, 1992).…”

Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue

“…Among the pRB family proteins, p107 and p130 are structurally closer to each other than to pRB and share unique properties allowing interaction with cyclins and Cdks Faha et al, 1992;Lees et al, 1992;Cobrinik et al, 1993;Zhu et al, 1995;Smith and Nevins, 1995). Through this interaction, p107 and p130 are capable of inhibiting the kinase activity of cyclin ± Cdk complexes (Zhu et al, 1995;Woo et al, 1997;Castano et al, 1998).…”