Effects of fibroblastic growth factor on protein degradation, the migration of non-histone proteins to the nucleus and DNA synthesis in diploid fibroblasts.
Stimulation of resting WI38 cells, prelabeled with [3H]leucine, with fibroblastic growth factor (FGF) or serum, caused increased nuclear translocation of [3H]non-histone proteins [( 3H]NHP) and DNA synthesis, and a parallel decrease of proteolysis. [3H]NHP migration was independent of protein synthesis. Fractionation of the nuclear proteins in a pH gradient of 2.5-6.5 showed that [3H]NHP fractions with high degradation rates in resting cells corresponded to the [3H]NHP fractions with high migration rates in stimulated cells, suggesting that degradation and migration of [3H]NHP are linked. FGF inhibited cellular uptake of [3H]chloroquine, suggesting that FGF inhibits NHP degradation via lysosomes. The lysosomotropic amine eserine had similar effects as FGF. It is proposed that FGF induces NHP migration to the nucleus by inhibiting their lysosomal degradation. FGF also caused migration of [3H]histones, however, the mechanism is not clear.
D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002738:Chloroquine / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D003470:Culture Media; D004261:DNA Replication / Q000187:drug effects*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D011506:Proteins / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D003470:Culture Media; D006657:Histones; D011506:Proteins; D005346:Fibroblast Growth Factors; D002738:Chloroquine