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N-myc regulates parkin expression.

Publication ,  Journal Article
West, AB; Kapatos, G; O'Farrell, C; Gonzalez-de-Chavez, F; Chiu, K; Farrer, MJ; Maidment, NT
Published in: J Biol Chem
July 9, 2004

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.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 9, 2004

Volume

279

Issue

28

Start / End Page

28896 / 28902

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tretinoin
  • Proto-Oncogene Proteins c-myc
  • Protein Binding
  • Promoter Regions, Genetic
  • Parkinson Disease
  • Mice
  • Humans
  • Genes, Reporter
  • Gene Expression Regulation
 

Citation

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ICMJE
MLA
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West, A. B., Kapatos, G., O’Farrell, C., Gonzalez-de-Chavez, F., Chiu, K., Farrer, M. J., & Maidment, N. T. (2004). N-myc regulates parkin expression. J Biol Chem, 279(28), 28896–28902. https://doi.org/10.1074/jbc.M400126200
West, Andrew B., Gregory Kapatos, Casey O’Farrell, Fanny Gonzalez-de-Chavez, Kelvin Chiu, Matthew J. Farrer, and Nigel T. Maidment. “N-myc regulates parkin expression.J Biol Chem 279, no. 28 (July 9, 2004): 28896–902. https://doi.org/10.1074/jbc.M400126200.
West AB, Kapatos G, O’Farrell C, Gonzalez-de-Chavez F, Chiu K, Farrer MJ, et al. N-myc regulates parkin expression. J Biol Chem. 2004 Jul 9;279(28):28896–902.
West, Andrew B., et al. “N-myc regulates parkin expression.J Biol Chem, vol. 279, no. 28, July 2004, pp. 28896–902. Pubmed, doi:10.1074/jbc.M400126200.
West AB, Kapatos G, O’Farrell C, Gonzalez-de-Chavez F, Chiu K, Farrer MJ, Maidment NT. N-myc regulates parkin expression. J Biol Chem. 2004 Jul 9;279(28):28896–28902.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 9, 2004

Volume

279

Issue

28

Start / End Page

28896 / 28902

Location

United States

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Tretinoin
  • Proto-Oncogene Proteins c-myc
  • Protein Binding
  • Promoter Regions, Genetic
  • Parkinson Disease
  • Mice
  • Humans
  • Genes, Reporter
  • Gene Expression Regulation