N-myc regulates parkin expression.

Published

Journal Article

Mutations in the parkin gene are common in early-onset and familial Parkinson's disease (PD), and the parkin protein interacts in the ubiquitin-proteasome system as an E3 ligase. However, the regulatory pathways that govern parkin expression are unknown. In this study, we showed that a phylogenetically conserved N-myc binding site in the bi-directional parkin promoter interacted with myc-family transcription factors in reporter assays, and N-myc bound to the parkin promoter in chromatin immunoprecipitation assays and repressed transcription activity. Parkin expression was inversely correlated with N-myc levels in the developing mouse and human brain, in human neuroblastoma cell lines with various levels of n-myc amplification, and in an inducible N-myc cell line. Although parkin and N-myc expression were dramatically altered upon retinoic acid-induced differentiation of a human neuroblastoma cell line, modulation of parkin expression did not significantly affect either rates of cellular proliferation or levels of cyclin E. Analysis of additional genes associated with familial PD revealed a shared basis of transcription regulation mediated by N-myc and the cell cycle. Our results, in combination with functional knowledge of the proteins encoded by these genes, suggest a common pathway linking together PD, the ubiquitin-proteasome system, and cell cycle control.

Full Text

Duke Authors

Cited Authors

  • West, AB; Kapatos, G; O'Farrell, C; Gonzalez-de-Chavez, F; Chiu, K; Farrer, MJ; Maidment, NT

Published Date

  • July 9, 2004

Published In

Volume / Issue

  • 279 / 28

Start / End Page

  • 28896 - 28902

PubMed ID

  • 15078880

Pubmed Central ID

  • 15078880

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M400126200

Language

  • eng

Conference Location

  • United States