The effects of concanavalin A and other agents on protein degradation and migration of non-histone proteins (NHP) to the nucleus in lymphocytes.
Concanavalin A (conA) inhibits the degradation of [3H]leucine-labeled cellular proteins of human lymphocytes. The lectin also stimulates the migration of non-histone proteins (NHP) from the cytoplasm to the nucleus. The increased nuclear level of NHP is associated with increased cellular binding of [3H]actinomycin D [(3H]AD). Decreased protein breakdown and increased migration of NHP are parallel events, i.e. both changes occur as a function of the lectin concentration and display a similar time course, suggesting that these events could be related. Similar effects are observed with fluoride, chloroquine and iodoacetate: these agents simultaneously decrease proteolysis and increase the nuclear level of NHP, associated with increased cellular [3H]AD binding. Fractionation of the acidic NHP according to pH 2.5-6.5 shows that proteins with a high degree of degradation in unstimulated cells correspond to proteins with a high degree of migration in conA-stimulated cells. A similar correlation was observed in fluoride-treated lymphocytes. conA, fluoride and iodoacetate decrease cellular [3H]chloroquine [(3H]CQ) accumulation, indicating a lysosomotropic effect. These and previously reported data suggest, but do not prove that conA inhibits degradation of cellular proteins via the lysosomal pathway. Ammonium chloride, methylamine and sodium azide also inhibit proteolysis and increase cellular [3H]AD binding; however, their effects are weak. On the basis of these observations it appears that lysosomal degradation and migration of NHP to the nucleus are linked; however, the mechanism of the linkage is unknown.
D000165:Acridine Orange / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology*; D003609:Dactinomycin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D011506:Proteins; D003208:Concanavalin A; D003609:Dactinomycin; D012969:Sodium Fluoride; D000165:Acridine Orange