To identify the mechanism of action of CIN, we examined the effects of CIN on life span in three mutants implicated in major longevity pathways.
The predominance of "normal" carboxysomes in the HncsoS4AB Km mutant implicated other carboxysome shell component(s) as potential vertex proteins.
Prophylactic administration of HMGB1-specific neutralising antibody conferred significant protection against hepatic I R injury in wild-type mice, but not in a TLR4-defective (C3H/HeJ) mutant, implicating TLR4 in HMGB1-mediated hepatic I R injury (Ref. 99).
A mutant protein implicated in disease can have multiple changes in its behavior in the network.
NOD1 mutants are implicated in disease to a lesser extent than NOD2 mutants.
As we have picked mutants of genes implicated in chromosome stability, mutant alleles that result in a nonfunctional protein, or reduction of function as displayed by decreased strain fitness, or increased sensitivity to DNA-damaging agents, are candidate mutations that might contribute to chromosome instability in tumor cells.
The increased susceptibility of wild-type B. pseudomallei cells to ceftazidime with the addition of nitrate, which was not seen in the Δ narG mutant, implicates anaerobic nitrate respiration and NarGHI in drug tolerance.
Likewise, of the proteins known to interact with the CTD, none that show altered expression in 5A mutant cells are implicated in the phenotypic changes observed.
To determine components required for TNF to cause death of cells expressing elevated RIPK3, we tested MEF lines that were mutant for proteins implicated in TNF signaling.
We have also shown that rapamycin promotes the clearance of other intracytoplasmic, disease-associated, aggregate-prone proteins, including mutant proteins associated with spinocerebellar ataxias, mutant forms of α-synuclein implicated in PD, and mutant tau responsible for FTD, thereby attenuating their toxicity (Berger et al., 2006; Menzies et al., 2006; Williams et al., 2006).
