Indeed deletion of the F508 residue, which represents the most prevalent mutation in the CFTR, causes a temperature sensitive folding defect leading to protein degradation by the endoplasmic reticulum associated degradation machinery [21].
Analyses were performed separately for the insulin-resistant and the insulin-sensitive groups (hyperinsulinemic insulin-sensitive/fasted insulin-sensitive fold change and hyperinsulinemic insulin-resistant/fasted insulin-resistant fold change).
These GFPs all displayed progenitor-like fluorescence spectra, temperature-sensitive folding, a reduced structural stability and, for the least stable variants, a reduced steady state abundance.
It is worth mentioning that our backbone flexibility measures are consistent with those from Elastic Network Models, which are sensitive to fold, but not sequence.
Resistant lines were also highly collaterally sensitive (17-fold) to dibutylphthalate.
Complete list of the 195 annotated differentially expressed genes in the intestine of insulin-resistant compared to insulin-sensitive subjects (Fold change > 1.2, P < 0.05).
Tighter binding could act to decrease the steady state concentration of presumably aggregation-prone or protease sensitive Im7 folding intermediates, thus increasing the Im7 level in the cell.
In addition, ubc13 and rad30 mutants were also highly sensitive (~4-fold higher than wild type), further suggesting the generation of Mn2+-induced DNA damage.
Using more severe parameter analysis, three genes are significantly and differently expressed in the intestine of insulin-resistant subjects compared to insulin-sensitive controls (fold change > 1.5 and FDR < 0.05).
