Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells

Cancer Res. 2003 Jul 15;63(14):3860-5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / metabolism
  • Fenretinide / pharmacology
  • Glucosyltransferases / genetics
  • Glucosyltransferases / metabolism*
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / metabolism
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroectodermal Tumors, Primitive, Peripheral / enzymology*
  • Neuroectodermal Tumors, Primitive, Peripheral / genetics
  • Neuroectodermal Tumors, Primitive, Peripheral / pathology
  • Sequence Homology, Amino Acid
  • Transfection


  • Antineoplastic Agents
  • Nerve Tissue Proteins
  • RTN1 protein, human
  • Fenretinide
  • Glucosyltransferases
  • ceramide glucosyltransferase