Selective uptake and degradation of c-Fos and v-Fos by rat liver lysosomes.
The transcription factor c-Fos is a short-lived protein and calpains and ubiquitin-dependent systems have been proposed to be involved in its degradation. In this report, we consider a lysosomal degradation pathway for c-Fos. Using a cell-free assay, we have found that freshly isolated lysosomes can take up and degrade c-Fos with high efficiency. v-Fos, the oncogenic counterpart of c-Fos, can also be taken up by lysosomes, yet the amount of incorporated protein is much lower. c-Fos uptake is independent of its phosphorylation state but it appears to be regulated by dimerization with differentially phosphorylated forms of c-Jun, while v-Fos escapes this regulation. Moreover, we show that c-Fos is immunologically detected in lysosomes isolated from the liver of rats treated with the protease inhibitor leupeptin. Altogether, these results suggest that lysosomes can also participate in the selective degradation of c-Fos in rat liver.
Aniento
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Dpt. Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Valencia, Burjassot, Spain.
Papavassiliou
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AG
Knecht
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E
Roche
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E
D000818:Animals; D002460:Cell Line; D002474:Cell-Free System; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011480:Protease Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000302:isolation & purification / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014357:Trypsin
D007976:Leupeptins; D016761:Oncogene Proteins v-fos; D011480:Protease Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D014357:Trypsin; C032854:leupeptin