E2F-1 binding affinity for pRb is not the only determinant of the E2F-1 activity

E2F-1 is the major cellular target of pRB and is regulated by pRB during cell proliferation. Interaction between pRB and E2F-1 is dependent on the phosphorylation status of pRB. Despite the fact that E2F-1 and pRB have antagonistic activities when they are overexpressed, the role of the E2F-1-pRB interaction in cell growth largely remains unknown. Ideally, it would be better to study the properties of a pRB mutant that fails to bind to E2F, but retains all other activities. To date, no pRB mutation has been characterized in sufficient detail to show that it specifically eliminates E2F binding but leaves other interactions intact. An alternative approach to this issue is to ask whether mutations that change E2F proteins binding affinity to pRB are sufficient to change cell growth in aspect of cell cycle and tumor formation. Therefore, we used the E2F-1 mutants including E2F-1/S332-7A, E2F-1/S375A, E2F-1/S403A, E2F-1/Y411A and E2F-1/L132Q that have different binding affinities for pRB to better understand the roles of the E2F-1 phosphorylation and E2F-1-pRB interaction in the cell cycle, as well as in transformation and gene expression. Data presented in this study suggests that in vivo phosphorylation at amino acids 332-337, 375 and 403 is important for the E2F-1 and pRB interaction in vivo. However, although E2F-1 mutants 332-7, 375 and 403 showed similar binding affinity to pRB, they showed different characteristics in transformation efficiency, G₀ accumulation, and target gene experiments.     

Adenovirus proteins that regulate susceptibility to TNF also regulate the activity of PLA2

Expression of the adenovirus E1A protein induces susceptibility to TNF. To counteract this effect, the adenovirus encodes a number of gene products that preserve host cell resistance to TNF. The E1B-19K protein, the E3 14.7 K protein, and the E3 10.4/14.5 K dimer each function in different cell types to provide resistance to TNF. Expression of E1A also results in the activation of PLA₂ and the release of arachidonic acid from the dying cell. The E3 14.7 K protein can prevent the activation of PLA₂, suggesting that in addition to providing host cell resistance to TNF, this protein also functions in an anti-inflammatory manner.     

Nods: a family of cytosolic proteins that regulate the host response to pathogens

Genetic variation in Nod2 is associated with susceptibility to Crohn's disease. Nod2 and its homologue, Nod1, are members of a growing family of cytosolic factors related to the apoptosis regulator Apaf-1 and a class of plant disease resistance proteins. Nod1 and Nod2 confer responsiveness to lipopolysaccharides and interact with RICK, a mediator of NF-kappaB activation. Nod1 and Nod2 and related Nods appear to regulate the host response to pathogens, a process that may be faulty in certain inflammatory diseases. Recent studies that suggest that Nods may be involved in the recognition of pathogen components in the cytosol of mammalian cells are reviewed.