title: Induction of Expression of p75 Neurotrophin Receptor Intracellular Domain Does Not Induce Expression or Enhance Activity of Mitochondrial Complex II.
abstract: Fenretinide is a chemotherapeutic agent in clinical trials for the treatment of neuroblastoma, among the most common and most deadly cancers of childhood. Fenretinide induces apoptosis in neuroblastoma cells through accumulation of mitochondrial reactive oxygen species released from Complex II. The neurotrophin receptor, p75NTR, potentiates this effect. The signaling activity of p75NTR is dependent upon its cleavage to its intracellular domain, p75ICD, trafficking of p75ICD to the nucleus, and functioning of p75ICD as a transcription factor. Mitochondrial Complex II comprises 4 subunits, all of which are encoded by nuclear DNA. We therefore hypothesized that the fenretinide-potentiating effects of p75NTR are the result of transcriptional enrichment of Complex II by p75ICD. However, the present studies demonstrate that neither induced expression of p75ICD or its active fragments nor overexpression of p75NTR results in altered expression or activity of Complex II.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Yaoli Pu
authors.initials: YP
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Lotta
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Gisela
authors.initials: G
authors.lastname: Beutner
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Nina F
authors.initials: NF
authors.lastname: Schor
mesh_terms: D000818:Animals; D042963:Electron Transport Complex II / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics; D041681:NIH 3T3 Cells; D017434:Protein Structure, Tertiary; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D042963:Electron Transport Complex II