Overexpression of P-glycoprotein, encoded by the MDR1 (multidrug resistance 1) 
gene, is often responsible for multidrug resistance and chemotherapy failure in 
cancer. We have demonstrated that, in leukaemic cells, P-glycoprotein expression 
is regulated at the translational level. More recently, we have shown that in 
cells overexpressing P-glycoprotein, MDR1 mRNA does not aggregate into 
translationally silent stress granules. Importantly, this is not unique for 
MDR1, since other transcripts encoding transmembrane proteins, and which are 
thus translated at the endoplasmic reticulum, follow the same pattern. By using 
a series of chimaeric transcripts, we have demonstrated that transcript 
localization at the endoplasmic reticulum bypasses the signals dictating stress 
granule sequestration. Polysome profile analyses and protein synthesis 
experiments indicate that, upon stress withdrawal, endoplasmic-reticulum-bound 
transcripts resume translation faster than those at the cytosol, which have been 
sequestered into stress granules. This may represent a novel mechanism by which 
drug-resistant cells respond quickly to stress, helping them to survive the 
cytotoxic effect of chemotherapeutic drugs.