Ceramide as an activator lipid of cathepsin D.
We have identified the aspartic protease cathepsin D as a novel intracellular target protein for the lipid second messenger ceramide. Ceramide specifically binds to and induces CTSD proteolytic activity. A-SMase deficient cells derived from Niemann-Pick patients show decreased CTSD activity that was reconstituted by transfection with A-SMase cDNA. Ceramide accumulation in cells derived from A-ceramidase defective Farber patients correlates with enhanced CTSD activity. These findings suggest that A-SMase-derived ceramide targets endolysosomal CTSD.
Heinrich
M
M
Institute of Immunology, University of Kiel, Germany.
Wickel
M
M
Winoto-Morbach
S
S
Schneider-Brachert
W
W
Weber
T
T
Brunner
J
J
Saftig
P
P
Peters
C
C
Krönke
M
M
Schütze
S
S
D000581:Amidohydrolases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D002402:Cathepsin D / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002461:Cell Line, Transformed; D055572:Ceramidases; D002518:Ceramides / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008214:Lymphocytes / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009542:Niemann-Pick Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D020298:U937 Cells / Q000378:metabolism
D002518:Ceramides; D016207:Cytokines; D018076:DNA, Complementary; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D013108:Sphingomyelin Phosphodiesterase; D002402:Cathepsin D; D000581:Amidohydrolases; D055572:Ceramidases