ADP-RIBOSYLATION OF THE MOLECULAR CHAPERONE GRP78 BIP/

Starvation of mouse hepatoma cells for essential amino acids or glucos e results in the ADP-ribosylation of the molecular chaperone BiP/GRP78 . Addition of the missing nutrient to the medium reverses the reaction . The signal mediating the response to environmental nutrients involve s the translational efficiency. An inhibitor of proteins synthesis, cy cloheximide, or reduced temperature, both of which reduce translationa l efficiency, stimulate the ADP-ribosylation of BiP/GRP78. Inhibition of N-linked glycosylation of proteins results in the overproduction of BiP/GRP78. The over produced protein is not ADP-ribosylated suggestin g that this is the functional form of BiP/GRP78. The over produced BiP /GRP78 can, however, be ADP-ribosylated if the cells are starved for a n essential amino acid. BiP/GRP78 resides in the lumen of the endoplas mic reticulum where it participates in the assembly of secretory and i ntegral membrane proteins. ADP-ribosylation of BiP/GRP78 during starva tion is probably part of a nutritional stress response which conserves limited nutrients by slowing flow through the secretory pathway.