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Identification of a novel gene linked to parkin via a bi-directional promoter.

Publication ,  Journal Article
West, AB; Lockhart, PJ; O'Farell, C; Farrer, MJ
Published in: J Mol Biol
February 7, 2003

Mutations of the parkin gene on chromosome 6q25-27 are the predominant genetic cause of early-onset and autosomal recessive juvenile parkinsonism. Parkin is a multi-domain protein with ubiquitin-protein E3 ligase activity that has a role in the proteasome-mediated degradation of target substrates. Although the parkin gene contains an expanded intron/exon structure and spans more than 1.3 Mb, we have identified a novel transcript that initiates 204 bp upstream of parkin and spans over 0.6 Mb, antisense to parkin. We have tentatively named this novel gene Parkin co-regulated gene, or PACRG. A 35 bp site of bi-directional transcription activation within the common promoter was mapped using dual-luciferase assays. This region appeared to be responsible for the majority of transcription regulation of both genes, and comparison of the mouse and human sequences revealed conserved transcription factor-binding sites. A 15 bp interval within the activation region, containing a non-canonical myc-binding site, bound nuclear protein derived from human substantia nigra. Database analysis identified highly conserved homologs of PACRG encoded by the mouse and Drosophila genomes, and Northern analysis demonstrated that PACRG and parkin were co-expressed in many tissues, including brain, heart and muscle. Western analysis revealed a protein of the predicted size, approximately 30 kDa, which was expressed in mouse and human brain. Although PACRG protein lacks known functional domains, in silico prediction suggests a potential link to the ubiquitin/proteasome system.

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Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

February 7, 2003

Volume

326

Issue

1

Start / End Page

11 / 19

Location

Netherlands

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transcription Factors
  • Substantia Nigra
  • Species Specificity
  • Response Elements
  • RNA, Messenger
  • Proteins
  • Promoter Regions, Genetic
  • Parkinson Disease
  • Molecular Sequence Data
 

Citation

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West, A. B., Lockhart, P. J., O’Farell, C., & Farrer, M. J. (2003). Identification of a novel gene linked to parkin via a bi-directional promoter. J Mol Biol, 326(1), 11–19. https://doi.org/10.1016/s0022-2836(02)01376-1
West, Andrew B., Paul J. Lockhart, Casey O’Farell, and Matthew J. Farrer. “Identification of a novel gene linked to parkin via a bi-directional promoter.J Mol Biol 326, no. 1 (February 7, 2003): 11–19. https://doi.org/10.1016/s0022-2836(02)01376-1.
West AB, Lockhart PJ, O’Farell C, Farrer MJ. Identification of a novel gene linked to parkin via a bi-directional promoter. J Mol Biol. 2003 Feb 7;326(1):11–9.
West, Andrew B., et al. “Identification of a novel gene linked to parkin via a bi-directional promoter.J Mol Biol, vol. 326, no. 1, Feb. 2003, pp. 11–19. Pubmed, doi:10.1016/s0022-2836(02)01376-1.
West AB, Lockhart PJ, O’Farell C, Farrer MJ. Identification of a novel gene linked to parkin via a bi-directional promoter. J Mol Biol. 2003 Feb 7;326(1):11–19.
Journal cover image

Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

February 7, 2003

Volume

326

Issue

1

Start / End Page

11 / 19

Location

Netherlands

Related Subject Headings

  • Ubiquitin-Protein Ligases
  • Transcription Factors
  • Substantia Nigra
  • Species Specificity
  • Response Elements
  • RNA, Messenger
  • Proteins
  • Promoter Regions, Genetic
  • Parkinson Disease
  • Molecular Sequence Data