Complex modulation of peptidolytic activity of cathepsin D by sphingolipids

0366668 - ÚOCHB 2012 RIV NL eng J - Journal Article
Žebrakovská, Iva - Máša, Martin - Srp, Jaroslav - Horn, Martin - Vávrová, K. - Mareš, Michael
Complex modulation of peptidolytic activity of cathepsin D by sphingolipids.
Biochimica Et Biophysica Acta-Molecular and Cell Biology of Lipids. Roč. 1811, č. 12 (2011), s. 1097-1104. ISSN 1388-1981. E-ISSN 1879-2618
R&D Projects: GA AV ČR IAA400550705
Institutional research plan: CEZ:AV0Z40550506
Keywords : sphingolipid * phospholipid * inhibition * activation * cathepsin D * enzyme regulation
Subject RIV: CE - Biochemistry
Impact factor: 5.269, year: 2011

Cathepsin D is an aspartic peptidase involved in cellular processes including proliferation and apoptosis. We describe a complex pattern of modulation of the peptidolytic activity of cathepsin D by sphingolipids. A panel of sphingolipid derivatives was screened in a FRET-based assay; these molecules demonstrated negative or positive modulation of cathepsin D peptidolytic activity, depending on the sphingolipid structure. Certain sphingosines and ceramides inhibited cathepsin D, and structural requirements for this inhibitory effect were evaluated. In contrast, monoester phosphosphingolipids, especially ceramide-1-phosphate, were identified as activators of cathepsin D peptidolytic activity Thus, sphingolipids and phosphosphingolipids, known to be antagonistic in their cell-signaling functions, displayed opposite modulation of cathepsin D.
Permanent Link: http://hdl.handle.net/11104/0201567