TY - JOUR
T1 - Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells
AU - Di Sano, Federica
AU - Fazi, Barbara
AU - Citro, Gennaro
AU - Lovat, Penny E.
AU - Cesareni, Gianni
AU - Piacentini, Mauro
PY - 2003/7/15
Y1 - 2003/7/15
N2 - Glucosylceramide synthase (GCS), the key enzyme in the biosynthesis of glycosphingolipids, has been implicated in many biological phenomena, including multidrug resistance. GCS inhibition, by both antisense and the specific inhibitor (D-threo)-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), results in a drastic decrease of apoptosis induced by the p53-independent chemotherapeutic agent N-(4-hydroxyphenyl)retinamide in neuroepithelioma cells. By using the yeast two-hybrid system, we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner. Interestingly, RTN-1C not only interacts with GCS at Golgi/ER interface but also modulates its catalytic activity in situ. In fact, overexpression of RTN-1C sensitizes CHP-100 cells to fenretinide-induced apoptosis. These findings demonstrate a novel p53-independent pathway of apoptosis regulated by Golgi/endoplasmic reticulum protein interactions, which is relevant for cancer combined therapy.
AB - Glucosylceramide synthase (GCS), the key enzyme in the biosynthesis of glycosphingolipids, has been implicated in many biological phenomena, including multidrug resistance. GCS inhibition, by both antisense and the specific inhibitor (D-threo)-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), results in a drastic decrease of apoptosis induced by the p53-independent chemotherapeutic agent N-(4-hydroxyphenyl)retinamide in neuroepithelioma cells. By using the yeast two-hybrid system, we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner. Interestingly, RTN-1C not only interacts with GCS at Golgi/ER interface but also modulates its catalytic activity in situ. In fact, overexpression of RTN-1C sensitizes CHP-100 cells to fenretinide-induced apoptosis. These findings demonstrate a novel p53-independent pathway of apoptosis regulated by Golgi/endoplasmic reticulum protein interactions, which is relevant for cancer combined therapy.
UR - http://www.scopus.com/inward/record.url?scp=0041742270&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041742270&partnerID=8YFLogxK
M3 - Article
C2 - 12873973
AN - SCOPUS:0041742270
VL - 63
SP - 3860
EP - 3865
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 14
ER -