NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells.

NCYM is a cis-antisense gene of MYCN and is amplified in human neuroblastomas. High NCYM expression is associated with poor prognoses, and the NCYM protein stabilizes MYCN to promote proliferation of neuroblastoma cells. However, the molecular mechanisms of NCYM in the regulation of cell survival have remained poorly characterized. Here we show that NCYM promotes cleavage of MYCN to produce the anti-apoptotic protein, Myc-nick, both in vitro and in vivo. NCYM and Myc-nick were induced at G2/M phase, and NCYM knockdown induced apoptotic cell death accompanied by Myc-nick downregulation. These results reveal a novel function of NCYM as a regulator of Myc-nick production in human neuroblastomas.
AuthorsWataru Shoji, Yusuke Suenaga, Yoshiki Kaneko, S M Rafiqul Islam, Jennifer Alagu, Sana Yokoi, Masaki Nio, Akira Nakagawara
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 461 Issue 3 Pg. 501-6 (Jun 5 2015) ISSN: 1090-2104 [Electronic] United States
PMID25896758 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • MYCN protein, human
  • Nuclear Proteins
  • Oncogene Proteins
  • Apoptosis
  • Cell Division
  • Cell Line, Tumor
  • G2 Phase
  • Genes, myc
  • Humans
  • In Situ Nick-End Labeling
  • Neuroblastoma (genetics, metabolism, pathology)
  • Nuclear Proteins (genetics)
  • Oncogene Proteins (genetics)
  • Real-Time Polymerase Chain Reaction

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