First, certain collateral signals might directly modulate p53 activity by changing the conformation of p53 or its association with various coactivators, perhaps leading to the expression of different subsets of p53 target genes.
Although it seems likely that a component of this response results from the ability of oncogenic Ras to produce quantitative increases in p53 activity via ARF-mediated inhibition of MDM2, there is compelling evidence for collateral signals that modify the outcome of p53 activation leading to senescence [17], [26].
TGF-β receptors can exert their effect through collateral signalling via mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) proteins [ 39].
For example, the effect of mTOR inhibition on upstream and downstream regulation within the PI3K-Akt and collateral signaling pathways has yet to be fully understood.
In an environment in which credit histories are not documented and pooled, the bank as a lender needs to expend significant time and resources on screening the loan applicant (Aleem 1990), while the borrower has limited means, such as collateral, to signal their trustworthiness (Stiglitz et al. 1992).
This specificity is unique to MuHV-4 and contrasts with other viral mechanisms of NF-κB inhibition that modulate upstream signalling events, such as the IKK complex, thus affecting collateral cellular signalling pathways.
For example, the ability to induce tumor regressions with tolerable doses of DNA-damaging cytotoxic agents might reflect underlying defects in DNA repair coupled with collateral pro-apoptotic signals delivered by oncoproteins such as E2F1 and c-Myc.
The idea of modulation of sensory processing exerted by internal collaterals of motor signals is well known (Sperry, 1950; Von Holst and Mittelstaedt, 1950).
Furthermore, collagenous structures, such as the collateral ligaments, may demonstrate increased signal intensity because of the 'magic angle' phenomenon, which may lead to overestimation of ligament pathology [ 45].
