Fierke, Christianson, and others found that mutations of the first shell of CA generally led to large (∼1000-fold ∼1000-fold in activity while mutations of the secondecreasesinactivityHis94 and His119 resulted in moderately (3−10-fold) lowhilecat/ Kmutationsbut, depending of the mutation, could modulate the p Ka of the zinc water/hydroxide nucleophile.
Whatever the impact of the W62L mutation in isolation, it seems possible that it could modulate translational efficiency to the lower level of activity seen in eIF4ER, when in combination with the other mutations.
Because MazG activity may mimic the effects of these mutations, it is possible that phage-encoded MazG could modulate the virulence and/or antibiotic tolerance of a lysogen.
We showed that under 1% O2 conditions, overexpression of Nur77 could potently enhance β-catenin in HCT116 cells normally expressing both APC and p53, as well as SW480 and HT29 cells with mutations in both APC and p53, suggesting that Nur77 could modulate β-catenin expression independent of APC and p53.
Environmental factors and/or the presence of a complex allele could modulate the initial consequence of the c.3909C>G mutation.
In theory, use of APC could modulate the effect of the Factor V Leiden mutation.
We speculated that posttranslational modifications of the DSG2 ICS segment may occur in vivo, which could modulate binding to other desmosomal proteins, and that the three mutations might influence such posttranslational modifications.
On the light of the role of Fbxo18 in HR, we speculate that the mutations reported in Fbxo18 might be relevant for the treatment of ovarian cancer and could modulate the response to PARP inhibitors.
Therefore, nongenetic events associated with HCD feeding could modulate tumor initiation when the latter is driven by a defined oncogenic mutation including KRAS (Guerra et al., 2007; Park et al., 2010a).
