Cellular and viral components that mediate glucocorticoid-regulated processing of retroviral envelope proteins

A comparison of the MMTV and MuLVenelope proteins in W7MG1 cells indicates that within the same cell some proteins are processed and sorted constitutively in the ER/Golgi system, whereas other proteins are processed in a hormone-dependent manner. The requisite hormone-dependent step in MMTV envelope protein processing occurs relatively early in the pathway, before the mannosidase II step (in the medial Golgi), which renders the oligosaccharide chains endo H resistant. Thus, the hormone dependent step must occur in the ER or early Golgi stacks; it cannot be proteolytic cleavage, any secondary glycosylation, sorting of proteins into specific secretory pathways (e.g., constitutive vs regulated), or transport to the cell surface, because all of these steps occur after acquisition of endo H resistance. The remaining candidates for the hormone-regulated step include core oligosaccharide trimming, subunit folding, subunit oligomerization (with homologous or heterologous proteins), or exit from the ER. Our current studies are focusing on these ER events. The proteolytic cleavage step for the MMTV envelope proteins occurs after acquisition of endo H resistance and after terminal galactose addition (in thetrans-Golgi). Although studies of the envelope proteins of several other retroviruses have concluded that proteolytic cleavage occurs before acquisition of endo H resistance, we suggest that these conclusions are premature without examination of processing intermediates. Finally, when the MMTV envelope gene is expressed in cells without any of the other MMTV genes, Pr74 is not processed to mature products. Although a point mutation in the envelope protein cannot be ruled out, we propose that the product of another MMTV gene may be required for the processing of Pr74.