title: NCYM promotes calpain-mediated Myc-nick production in human MYCN-amplified neuroblastoma cells.
abstract: 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.
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan; Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Shoji
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan; Cancer Genome Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan. Electronic address: ysuenaga@chiba-cc.jp.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suenaga
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: S M Rafiqul
authors.initials: SM
authors.lastname: Islam
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Alagu
authors.affiliation: Cancer Genome Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan.
authors.forename: Sana
authors.initials: S
authors.lastname: Yokoi
authors.affiliation: Department of Pediatric Surgery, Graduate School of Medicine, Tohoku University, Sendai 980-8574, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nio
authors.affiliation: Division of Biochemistry and Innovative Cancer Therapeutics and Children's Cancer Research Center, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuo-ku, Chiba 260-8717, Japan. Electronic address: nakagawara-a@koseikan.jp.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D016195:G2 Phase; D016259:Genes, myc; D006801:Humans; D020287:In Situ Nick-End Labeling; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins
keywords: Calpain; Cell cycle; MYCN; Myc-nick; NCYM; Neuroblastoma