Moreover, several studies have described the accumulation of mutant PrP molecules associated with hereditary PrDs at the ER and Golgi [7], [10], [11], [14], [15], [16], suggesting that some prion mutants may exert their pathological effects by affecting these organelles.
Together with findings that the effect of respiratory-chain RNAi and respiration mutants may exert different outputs in gene expression and metabolism [ 11, 13], these studies suggest that there are additional mechanisms by which impaired ETC function (in particular that induced by RNAi) increases life span.
To provide an independent line of evidence that NBD1, and disease relevantly, its ΔF508 mutant, may exert an allosteric regulation of CK2, their ability to physically interact with CK2 subunits was assessed by the SPR technique using surface plasmon resonance.
Recently, fluorescently tagging wildtype and mutant SOD1 with green fluorescent protein (GFP) or yellow fluorescent protein (YFP), to examine its intracellular localization, has become a well used method to explore possible novel mechanisms by which mutant SOD1 may exert its toxic effects.
In this context, mutant desmin may exert a pathogenic effect on the viscoelastic properties of the desmin filament system, which consecutively may lead to progressive muscle fiber damage and muscle weakness.
This was not unexpected as it is well known that mutant p53 may exert a dominant negative effect by preventing wt p53 from binding to the promoter of its target genes.
However, studies into UPS function in various polyglutamine disease models have yielded conflicting results, suggesting mutant polyglutamine tracts may exert different effects on the UPS depending on protein context, expression level, subcellular localisation and cell-type.
These studies suggest that mutant p53 proteins may exert still unknown effects on cellular metabolism, either independently or via the inactivation of p53 family members, which may promote tumor development.
We assumed that denaturation by heat stress may disrupt the aberrant conformation of the p53 mutant, and glycerol may exert its effect during renaturation to stabilize the transient wtp53 conformation that is otherwise very unstable.
The striking phenotypes of these mutants suggest that MPT5 may exert its effects through regulation of the fMAPK pathway.
This restoration of exoproducts was not observed in an rhlR mutant, which suggests that PqsE may exert its effects through the rhl system (Farrow et al., 2008).
