ABSTRACT
Binding Protein ............................................................................................. 131 10.4 Relationship of GRP78 and GRP94 and Heat Shock Proteins ..................... 132 10.5 Link of GRP78 to Cancer ............................................................................. 133 10.6 Link of GRP94 to Cancer Immunogenicity ................................................. 135 10.7 Conclusion .................................................................................................... 135 Acknowledgments .................................................................................................. 136 References .............................................................................................................. 136
The story of the discovery of the glucose-regulated proteins GRP78 and GRP94 began in 1974 when virologists first noticed changes in the protein profile when they transformed chick embryo fibroblasts and NRK cells with avian sarcoma viruses (1,2). In particular, the synthesis of the two proteins with molecular masses of 75 and 90 kilodaltons (kDa) were greatly enhanced. These proteins were originally thought to be transformation-specific proteins. As such, they could serve very important functions in converting a normal cell into the cancerous state. However, further investigation into the nature of induction of these proteins by the I. Pastan laboratory at the National Cancer Institute revealed that they were not encoded by the retroviruses; rather, they were cellular proteins synthesized constitutively in varying amounts under tissue culture conditions or in whole organs (3). Moreover, the accumulation of these same proteins could occur by simply culturing the cells in medium
deprived of glucose in the absence of viral transformation. Thus, reinterpretation of the original observations would suggest that accumulation of these proteins was not directly due to the onset of transformation; rather, their induction was a consequence of glucose deprivation from the culture medium by the rapidly growing transformed cells (3). Because the synthesis of these proteins was regulated by the concentration of glucose in the culture medium, the 78-and 94-kDa proteins were named glucose regulated proteins GRP78 and GRP94, respectively.
