The SCF(Fbw7) ubiquitin ligase complex plays important roles in cell growth, 
survival, and differentiation via the ubiquitin-proteasome-mediated regulation 
of protein stability. Fbw7 (also known as Fbxw7, Sel-10, hCdc4, or hAgo), a 
substrate recognition subunit of SCF(Fbw7) ubiquitin ligase, facilitates the 
degradation of several proto-oncogene products by the proteasome. Given that 
mutations in Fbw7 are found in various types of human cancers, Fbw7 is 
considered to be a potent tumor suppressor. In the present study, we show that 
E1A, an oncogene product derived from adenovirus, interferes with the activity 
of the SCF(Fbw7) ubiquitin ligase. E1A interacted with SCF(Fbw7) and attenuated 
the ubiquitylation of its target proteins in vivo. Furthermore, using in vitro 
purified SCF(Fbw7) component proteins, we found that E1A directly bound to 
Roc1/Rbx1 and CUL1 and that E1A inhibited the ubiquitin ligase activity of the 
Roc1/Rbx1-CUL1 complex but not that of another RING-type ubiquitin ligase, Mdm2. 
Ectopically expressed E1A interacted with cellular endogenous Roc1/Rbx1 and CUL1 
and decelerated the degradation of several protooncogene products that were 
degraded by SCF(Fbw7) ubiquitin ligase. Moreover, after wild-type adenovirus 
infection, adenovirus-derived E1A interacted with endogenous Roc1/Rbx1 and 
decelerated degradation of the endogenous target protein of SCF(Fbw7). These 
observations demonstrated that E1A perturbs protein turnover regulated by 
SCF(Fbw7) through the inhibition of SCF(Fbw7) ubiquitin ligase. Our findings may 
help to explain the mechanism whereby adenovirus infection induces unregulated 
proliferation.