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Gewählte Publikation:

Schähs, P; Weidinger, P; Probst, OC; Svoboda, B; Stadlmann, J; Beug, H; Waerner, T; Mach, L.
(2008): Cellular repressor of E1A-stimulated genes is a bona fide lysosomal protein which undergoes proteolytic maturation during its biosynthesis.
Exp Cell Res. 2008; 314(16):3036-3047 FullText FullText_BOKU

Cellular repressor of E1A-stimulated genes (CREG) has been reported to be a secretory glycoprotein implicated in cellular growth and differentiation. We now show that CREG is predominantly localized within intracellular compartments. Intracellular CREG was found to lack an N-terminal peptide present in the secreted form of the protein. In contrast to normal cells, CREG is largely secreted by fibroblasts missing both mannose 6-phosphate receptors. This is not observed in cells lacking only one of them. Mass spectrometric analysis of recombinant CREG revealed that the protein contains phosphorylated oligosaccharides at either of its two N-glycosylation sites. Cellular CREG was found to cosediment with lysosomal markers upon subcellular fractionation by density-gradient centrifugation. In fibroblasts expressing a CREG-GFP fusion construct, the heterologous protein was detected in compartments containing lysosomal proteins. Immunolocalization of endogenous CREG confirmed that intracellular CREG is localized in lysosomes. Proteolytic processing of intracellular CREG involves the action of lysosomal cysteine proteinases. These results establish that CREG is a lysosomal protein that undergoes proteolytic maturation in the course of its biosynthesis, carries the mannose 6-phosphate recognition marker and depends on the interaction with mannose 6-phosphate receptors for efficient delivery to lysosomes. (C) 2008 Elsevier Inc. All rights reserved.
Autor*innen der BOKU Wien:
Mach Lukas
Stadlmann Johannes
BOKU Gendermonitor:

Find related publications in this database (using NML MeSH Indexing)
Animals -
COS Cells -
Cercopithecus aethiops -
Cysteine Endopeptidases - metabolism
Glycosylation -
Humans -
Insects -
Lysosomes - chemistry
Mannosephosphates - chemistry
Mass Spectrometry -
Mice -
Oligosaccharides - chemistry
Peptides - genetics
Protease Inhibitors - metabolism
Protein Processing, Post-Translational -
Receptor, IGF Type 2 - genetics
Recombinant Fusion Proteins - chemistry
Repressor Proteins - chemistry

Find related publications in this database (Keywords)
mannose 6-phosphate
protein targeting
proteolytic maturation

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