Effects of inhibitors of glycoprotein processing on the synthesis and biological activity of the erb B oncogene.
Three glycoprotein-processing inhibitors were used to resolve whether correct glycosylation was required for the oncogenic activity of erb B. The two glucosidase-I inhibitors, 1-deoxynojirimycin and 2,5-dihydroxymethyl 3,4-dihydroxypyrrolidine, arrested processing of v-erb B at the immature 68-kd form whereas, in the presence of the alpha-mannosidase-II inhibitor (swainsonine), cells synthesised an abnormally processed 70-kd form of v-erb B. Transport of incorrectly processed v-erb B to the cell surface was, however, unaffected, suggesting that correct processing is not a prerequisite for intracellular routing of v-erb B. Two systems were used to assess whether incorrectly processed erb B could maintain the transformed state. The first asked whether inhibitor treatment would release temperature-sensitive avian erythroblastosis virus (AEV) transformed erythroblasts kept at the viral permissive temperature from the erb B-induced block in differentiation, as seen when cells are normally shifted to the non-permissive temperature. The second tested the ability of AEV-transformed fibroblasts to grow in soft agar. In both systems, all three processing inhibitors did not alter the transformed phenotype suggesting that correct carbohydrate processing is not required for the transforming activity of erb B. In addition, none of the three processing inhibitors were found to have any effect on the normal maturation of bone marrow CFU-E or induced differentiation of temperature-sensitive AEV-transformed erythroblasts.
Schmidt
J A
JA
Beug
H
H
Hayman
M J
MJ
D000470:Alkaloids / Q000494:pharmacology; D001355:Alpharetrovirus / Q000235:genetics*; D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002645:Chickens; D004900:Erythroblasts; D006023:Glycoproteins / Q000378:metabolism*; D065089:Glycoside Hydrolase Inhibitors; D009857:Oncogenes; D017026:Swainsonine; D014764:Viral Proteins / Q000096:biosynthesis; D000520:alpha-Glucosidases
D000470:Alkaloids; D006023:Glycoproteins; D065089:Glycoside Hydrolase Inhibitors; D014764:Viral Proteins; C042059:glucosidase I; D000520:alpha-Glucosidases; D017026:Swainsonine